Comprehensive Physiology Wiley Online Library

Extracellular Matrix Stiffness in Lung Health and Disease

Full Article on Wiley Online Library


The extracellular matrix (ECM) provides structural support and imparts a wide variety of environmental cues to cells. In the past decade, a growing body of work revealed that the mechanical properties of the ECM, commonly known as matrix stiffness, regulate the fundamental cellular processes of the lung. There is growing appreciation that mechanical interplays between cells and associated ECM are essential to maintain lung homeostasis. Dysregulation of ECM‐derived mechanical signaling via altered mechanosensing and mechanotransduction pathways is associated with many common lung diseases. Matrix stiffening is a hallmark of lung fibrosis. The stiffened ECM is not merely a sequelae of lung fibrosis but can actively drive the progression of fibrotic lung disease. In this article, we provide a comprehensive view on the role of matrix stiffness in lung health and disease. We begin by summarizing the effects of matrix stiffness on the function and behavior of various lung cell types and on regulation of biomolecule activity and key physiological processes, including host immune response and cellular metabolism. We discuss the potential mechanisms by which cells probe matrix stiffness and convert mechanical signals to regulate gene expression. We highlight the factors that govern matrix stiffness and outline the role of matrix stiffness in lung development and the pathogenesis of pulmonary fibrosis, pulmonary hypertension, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. We envision targeting of deleterious matrix mechanical cues for treatment of fibrotic lung disease. Advances in technologies for matrix stiffness measurements and design of stiffness‐tunable matrix substrates are also explored. © 2022 American Physiological Society. Compr Physiol 12:3523‐3558, 2022.

Figure 1. Figure 1. A scheme of matrix stiffness‐mediated mechanosensing and mechanotransduction pathways. ECM‐derived mechanical cues are sensed by cell surface receptors, including integrin‐containing FAs, GPCRs, and TRPV4. Mechanoactivation of RhoA and ROCK promotes G‐actin polymerization into F‐actin, resulting in the release of MKL1 and its nuclear translocation. RhoA/ROCK activation and the remodeling of actin cytoskeleton can also activate YAP/TAZ and promote their nuclear translocation, whereas the canonical Hippo signaling phosphorylates YAP/TAZ and inhibits their nuclear translocation. In the nucleus, MKL1 interacts with SRF to activate the transcription of target genes, including αSMA and BCL2. MKL1 binds to YAP, which regulates CCN1 gene expression. In contrast, MKL1 and TAZ appear to antagonize each other for the cytoplasmic‐nuclear shuttling and the binding of gene promoter. MKL1 also regulates histone modifications through binding to H3K4 methyltransferase. Other mechanosensitive transcription factors include NF‐κB, β‐catenin, c‐Fos/c‐Jun, STAT3, ZNF416, and ELK1. Furthermore, the contractile cytoskeleton pulling on a stiffened ECM may change the conformation of latent TGF‐β complex, leading to the release or exposure of active TGF‐β.
Figure 2. Figure 2. Mechanical testing of normal and fibrotic mouse lung tissues by AFM microindentation. (A) A MFP‐3D‐BIO atomic force microscope (Asylum Research) mounted on a Nikon eclipse Ti2 microscope. (B) A typical force‐distance curve generated by AFM on mouse lung tissues. (C to E) C57BL/6 mice were administered 1.5 U/kg body weight bleomycin intratracheally to induce lung fibrosis. Control mice were given an equal volume (50 μL) of saline. Lung tissues were harvested at 28 d. Mechanical testing of unfixed native mouse lung tissues was performed by AFM microindentation. Tissue sections were stained with a collagen‐Col‐F collagen‐binding reagent to facilitate localization of specific lung areas (e.g., the alveolar wall and collagen‐enriched fibrotic area) and positioning of the cantilever tip (C). Heat maps show the elastic moduli (Young's moduli) of the alveolar wall in the saline‐treated lungs and the fibrotic area in bleomycin‐treated lungs (D). Bar graphs show the distribution of stiffness in saline‐ and bleomycin‐treated mouse lungs (E). Scale bars = 100 μm. (Panels C‐E: Reused, with permission, from Sato S, et al., 2021, 332)

Figure 1. A scheme of matrix stiffness‐mediated mechanosensing and mechanotransduction pathways. ECM‐derived mechanical cues are sensed by cell surface receptors, including integrin‐containing FAs, GPCRs, and TRPV4. Mechanoactivation of RhoA and ROCK promotes G‐actin polymerization into F‐actin, resulting in the release of MKL1 and its nuclear translocation. RhoA/ROCK activation and the remodeling of actin cytoskeleton can also activate YAP/TAZ and promote their nuclear translocation, whereas the canonical Hippo signaling phosphorylates YAP/TAZ and inhibits their nuclear translocation. In the nucleus, MKL1 interacts with SRF to activate the transcription of target genes, including αSMA and BCL2. MKL1 binds to YAP, which regulates CCN1 gene expression. In contrast, MKL1 and TAZ appear to antagonize each other for the cytoplasmic‐nuclear shuttling and the binding of gene promoter. MKL1 also regulates histone modifications through binding to H3K4 methyltransferase. Other mechanosensitive transcription factors include NF‐κB, β‐catenin, c‐Fos/c‐Jun, STAT3, ZNF416, and ELK1. Furthermore, the contractile cytoskeleton pulling on a stiffened ECM may change the conformation of latent TGF‐β complex, leading to the release or exposure of active TGF‐β.

Figure 2. Mechanical testing of normal and fibrotic mouse lung tissues by AFM microindentation. (A) A MFP‐3D‐BIO atomic force microscope (Asylum Research) mounted on a Nikon eclipse Ti2 microscope. (B) A typical force‐distance curve generated by AFM on mouse lung tissues. (C to E) C57BL/6 mice were administered 1.5 U/kg body weight bleomycin intratracheally to induce lung fibrosis. Control mice were given an equal volume (50 μL) of saline. Lung tissues were harvested at 28 d. Mechanical testing of unfixed native mouse lung tissues was performed by AFM microindentation. Tissue sections were stained with a collagen‐Col‐F collagen‐binding reagent to facilitate localization of specific lung areas (e.g., the alveolar wall and collagen‐enriched fibrotic area) and positioning of the cantilever tip (C). Heat maps show the elastic moduli (Young's moduli) of the alveolar wall in the saline‐treated lungs and the fibrotic area in bleomycin‐treated lungs (D). Bar graphs show the distribution of stiffness in saline‐ and bleomycin‐treated mouse lungs (E). Scale bars = 100 μm. (Panels C‐E: Reused, with permission, from Sato S, et al., 2021, 332)
 1.Adlerz KM, Aranda‐Espinoza H, Hayenga HN. Substrate elasticity regulates the behavior of human monocyte‐derived macrophages. Eur Biophys J 45: 301‐309, 2016.
 2.Alcaraz J, Buscemi L, Grabulosa M, Trepat X, Fabry B, Farré R, Navajas D. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys J 84: 2071‐2079, 2003.
 3.Allen RJ, Porte J, Braybrooke R, Flores C, Fingerlin TE, Oldham JM, Guillen‐Guio B, Ma SF, Okamoto T, John AE, Obeidat M, Yang IV, Henry A, Hubbard RB, Navaratnam V, Saini G, Thompson N, Booth HL, Hart SP, Hill MR, Hirani N, Maher TM, McAnulty RJ, Millar AB, Molyneaux PL, Parfrey H, Rassl DM, Whyte MKB, Fahy WA, Marshall RP, Oballa E, Bossé Y, Nickle DC, Sin DD, Timens W, Shrine N, Sayers I, Hall IP, Noth I, Schwartz DA, Tobin MD, Wain LV, Jenkins RG. Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: A genome‐wide association study. Lancet Respir Med 5: 869‐880, 2017.
 4.Allison DD, Grande‐Allen KJ. Review. Hyaluronan: A powerful tissue engineering tool. Tissue Eng 12: 2131‐2140, 2006.
 5.An SS, Mitzner W, Tang WY, Ahn K, Yoon AR, Huang J, Kilic O, Yong HM, Fahey JW, Kumar S, Biswal S, Holgate ST, Panettieri RA, Solway J, Liggett SB. An inflammation‐independent contraction mechanophenotype of airway smooth muscle in asthma. J Allergy Clin Immunol 138: 294‐297.e294, 2016.
 6.Anguiano M, Morales X, Castilla C, Pena AR, Ederra C, Martínez M, Ariz M, Esparza M, Amaveda H, Mora M. The use of mixed collagen‐Matrigel matrices of increasing complexity recapitulates the biphasic role of cell adhesion in cancer cell migration: ECM sensing, remodeling and forces at the leading edge of cancer invasion. PloS one 15: e0220019, 2020.
 7.Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci 116: 217‐224, 2003.
 8.Aragona M, Panciera T, Manfrin A, Giulitti S, Michielin F, Elvassore N, Dupont S, Piccolo S. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin‐processing factors. Cell 154: 1047‐1059, 2013.
 9.Araujo BB, Dolhnikoff M, Silva LF, Elliot J, Lindeman JH, Ferreira DS, Mulder A, Gomes HA, Fernezlian SM, James A, Mauad T. Extracellular matrix components and regulators in the airway smooth muscle in asthma. Eur Respir J 32: 61‐69, 2008.
 10.Asano S, Ito S, Takahashi K, Furuya K, Kondo M, Sokabe M, Hasegawa Y. Matrix stiffness regulates migration of human lung fibroblasts. Physiol Rep 5, 5 (9): e13281, 2017.
 11.Asparuhova MB, Ferralli J, Chiquet M, Chiquet‐Ehrismann R. The transcriptional regulator megakaryoblastic leukemia‐1 mediates serum response factor‐independent activation of tenascin‐C transcription by mechanical stress. FASEB J 25: 3477‐3488, 2011.
 12.Aumiller V, Strobel B, Romeike M, Schuler M, Stierstorfer BE, Kreuz S. Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis. Sci Rep 7: 149, 2017.
 13.Austen K, Ringer P, Mehlich A, Chrostek‐Grashoff A, Kluger C, Klingner C, Sabass B, Zent R, Rief M, Grashoff C. Extracellular rigidity sensing by talin isoform‐specific mechanical linkages. Nat Cell Biol 17: 1597‐1606, 2015.
 14.Aydin D, Louban I, Perschmann N, Blümmel J, Lohmüller T, Cavalcanti‐Adam EA, Haas TL, Walczak H, Kessler H, Fiammengo R, Spatz JP. Polymeric substrates with tunable elasticity and nanoscopically controlled biomolecule presentation. Langmuir 26: 15472‐15480, 2010.
 15.Azeloglu EU, Bhattacharya J, Costa KD. Atomic force microscope elastography reveals phenotypic differences in alveolar cell stiffness. J Appl Physiol 105 (652‐661): 2008, 1985.
 16.Balestrini JL, Chaudhry S, Sarrazy V, Koehler A, Hinz B. The mechanical memory of lung myofibroblasts. Integr Biol (Camb) 4: 410‐421, 2012.
 17.Bao M, Xie J, Huck WTS. Recent advances in engineering the stem cell microniche in 3D. Adv Sci (Weinh) 5: 1800448, 2018.
 18.Barriga EH, Franze K, Charras G, Mayor R. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo. Nature 554: 523‐527, 2018.
 19.Barry‐Hamilton V, Spangler R, Marshall D, McCauley S, Rodriguez HM, Oyasu M, Mikels A, Vaysberg M, Ghermazien H, Wai C, Garcia CA, Velayo AC, Jorgensen B, Biermann D, Tsai D, Green J, Zaffryar‐Eilot S, Holzer A, Ogg S, Thai D, Neufeld G, Van Vlasselaer P, Smith V. Allosteric inhibition of lysyl oxidase‐like‐2 impedes the development of a pathologic microenvironment. Nat Med 16: 1009‐1017, 2010.
 20.Bashirzadeh Y, Chatterji S, Palmer D, Dumbali S, Qian S, Maruthamuthu V. Stiffness measurement of soft silicone substrates for mechanobiology studies using a widefield fluorescence microscope. J Vis Exp, 2018.
 21.Basu R, Whitlock BM, Husson J, Le Floc'h A, Jin W, Oyler‐Yaniv A, Dotiwala F, Giannone G, Hivroz C, Biais N, Lieberman J, Kam LC, Huse M. Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing. Cell 165: 100‐110, 2016.
 22.Beenakker JW, Ashcroft BA, Lindeman JH, Oosterkamp TH. Mechanical properties of the extracellular matrix of the aorta studied by enzymatic treatments. Biophys J 102: 1731‐1737, 2012.
 23.Bellaye PS, Shimbori C, Upagupta C, Sato S, Shi W, Gauldie J, Ask K, Kolb M. Lysyl Oxidase‐like 1 protein deficiency protects mice from adenoviral transforming growth factor‐β1‐induced pulmonary fibrosis. Am J Respir Cell Mol Biol 58: 461‐470, 2018.
 24.Bellmunt MJ, Portero M, Pamplona R, Cosso L, Odetti P, Prat J. Evidence for the Maillard reaction in rat lung collagen and its relationship with solubility and age. Biochim Biophys Acta 1272: 53‐60, 1995.
 25.Bercoff J, Tanter M, Fink M. Supersonic shear imaging: A new technique for soft tissue elasticity mapping. IEEE Trans Ultrason Ferroelectr Freq Control 51: 396‐409, 2004.
 26.Berg WA, Cosgrove DO, Doré CJ, Schäfer FK, Svensson WE, Hooley RJ, Ohlinger R, Mendelson EB, Balu‐Maestro C, Locatelli M, Tourasse C, Cavanaugh BC, Juhan V, Stavros AT, Tardivon A, Gay J, Henry JP, Cohen‐Bacrie C, Investigators B. Shear‐wave elastography improves the specificity of breast US: The BE1 multinational study of 939 masses. Radiology 262: 435‐449, 2012.
 27.Berry MF, Engler AJ, Woo YJ, Pirolli TJ, Bish LT, Jayasankar V, Morine KJ, Gardner TJ, Discher DE, Sweeney HL. Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. Am J Physiol Heart Circ Physiol 290: H2196‐H2203, 2006.
 28.Bertero T, Cottrill KA, Lu Y, Haeger CM, Dieffenbach P, Annis S, Hale A, Bhat B, Kaimal V, Zhang YY, Graham BB, Kumar R, Saggar R, Wallace WD, Ross DJ, Black SM, Fratz S, Fineman JR, Vargas SO, Haley KJ, Waxman AB, Chau BN, Fredenburgh LE, Chan SY. Matrix remodeling promotes pulmonary hypertension through feedback mechanoactivation of the YAP/TAZ‐miR‐130/301 circuit. Cell Rep 13: 1016‐1032, 2015.
 29.Bertero T, Handen AL, Chan SY. Factors associated with heritable pulmonary arterial hypertension exert convergent actions on the miR‐130/301‐vascular matrix feedback loop. Int J Mol Sci 19: 2289, 2018.
 30.Bertero T, Oldham WM, Cottrill KA, Pisano S, Vanderpool RR, Yu Q, Zhao J, Tai Y, Tang Y, Zhang YY, Rehman S, Sugahara M, Qi Z, Gorcsan J, Vargas SO, Saggar R, Wallace WD, Ross DJ, Haley KJ, Waxman AB, Parikh VN, De Marco T, Hsue PY, Morris A, Simon MA, Norris KA, Gaggioli C, Loscalzo J, Fessel J, Chan SY. Vascular stiffness mechanoactivates YAP/TAZ‐dependent glutaminolysis to drive pulmonary hypertension. J Clin Invest 126: 3313‐3335, 2016.
 31.Bertero T, Oldham WM, Grasset EM, Bourget I, Boulter E, Pisano S, Hofman P, Bellvert F, Meneguzzi G, Bulavin DV, Estrach S, Feral CC, Chan SY, Bozec A, Gaggioli C. Tumor‐stroma mechanics coordinate amino acid availability to sustain tumor growth and malignancy. Cell Metab 29: 124‐140.e110, 2019.
 32.Besse F, Ephrussi A. Translational control of localized mRNAs: Restricting protein synthesis in space and time. Nat Rev Mol Cell Biol 9: 971‐980, 2008.
 33.Bhowmick NA, Moses HL. Tumor–stroma interactions. Curr Opin Genet Develop 15: 97‐101, 2005.
 34.Bidan CM, Veldsink AC, Meurs H, Gosens R. Airway and extracellular matrix mechanics in COPD. Front Physiol 6: 346, 2015.
 35.Bilgen M, Insana MF. Deformation models and correlation analysis in elastography. J Acoust Soc Am 99: 3212‐3224, 1996.
 36.Binnig G, Quate CF, Gerber C. Atomic force microscope. Phys Rev Lett 56: 930‐933, 1986.
 37.Birukova AA, Tian X, Cokic I, Beckham Y, Gardel ML, Birukov KG. Endothelial barrier disruption and recovery is controlled by substrate stiffness. Microvasc Res 87: 50‐57, 2013.
 38.Bischof JC, He X. Thermal stability of proteins. Ann N Y Acad Sci 1066: 12‐33, 2005.
 39.Blin G, Lablack N, Louis‐Tisserand M, Nicolas C, Picart C, Pucéat M. Nano‐scale control of cellular environment to drive embryonic stem cells selfrenewal and fate. Biomaterials 31: 1742‐1750, 2010.
 40.Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15: 786‐801, 2014.
 41.Booth AJ, Hadley R, Cornett AM, Dreffs AA, Matthes SA, Tsui JL, Weiss K, Horowitz JC, Fiore VF, Barker TH, Moore BB, Martinez FJ, Niklason LE, White ES. Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am J Respir Crit Care Med, 2012.
 42.Bordeleau F, Califano JP, Negrón Abril YL, Mason BN, LaValley DJ, Shin SJ, Weiss RS, Reinhart‐King CA. Tissue stiffness regulates serine/arginine‐rich protein‐mediated splicing of the extra domain B‐fibronectin isoform in tumors. Proc Natl Acad Sci U S A 112: 8314‐8319, 2015.
 43.Bordeleau F, Mason BN, Lollis EM, Mazzola M, Zanotelli MR, Somasegar S, Califano JP, Montague C, LaValley DJ, Huynh J, Mencia‐Trinchant N, Negrón Abril YL, Hassane DC, Bonassar LJ, Butcher JT, Weiss RS, Reinhart‐King CA. Matrix stiffening promotes a tumor vasculature phenotype. Proc Natl Acad Sci U S A 114: 492‐497, 2017.
 44.Boudreau N, Werb Z, Bissell MJ. Suppression of apoptosis by basement membrane requires three‐dimensional tissue organization and withdrawal from the cell cycle. Proc Natl Acad Sci U S A 93: 3509‐3513, 1996.
 45.Bourke JE, Li X, Foster SR, Wee E, Dagher H, Ziogas J, Harris T, Bonacci JV, Stewart AG. Collagen remodelling by airway smooth muscle is resistant to steroids and β2‐agonists. Eur Respir J 37: 173‐182, 2011.
 46.Branco da Cunha C, Klumpers DD, Koshy ST, Weaver JC, Chaudhuri O, Seruca R, Carneiro F, Granja PL, Mooney DJ. CD44 alternative splicing in gastric cancer cells is regulated by culture dimensionality and matrix stiffness. Biomaterials 98: 152‐162, 2016.
 47.Broguiere N, Isenmann L, Zenobi‐Wong M. Novel enzymatically cross‐linked hyaluronan hydrogels support the formation of 3D neuronal networks. Biomaterials 99: 47‐55, 2016.
 48.Brown AC, Fiore VF, Sulchek TA, Barker TH. Physical and chemical microenvironmental cues orthogonally control the degree and duration of fibrosis‐associated epithelial‐to‐mesenchymal transitions. J Pathol 229: 25‐35, 2013.
 49.Brown XQ, Bartolak‐Suki E, Williams C, Walker ML, Weaver VM, Wong JY. Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: Implications for atherosclerosis. J Cell Physiol 225: 115‐122, 2010.
 50.Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 318: 1315‐1321, 1988.
 51.Burdick JA, Anseth KS. Photoencapsulation of osteoblasts in injectable RGD‐modified PEG hydrogels for bone tissue engineering. Biomaterials 23: 4315‐4323, 2002.
 52.Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications. Adv Mater 23: H41‐H56, 2011.
 53.Butcher DT, Alliston T, Weaver VM. A tense situation: Forcing tumour progression. Nat Rev Cancer 9: 108‐122, 2009.
 54.Buxboim A, Irianto J, Swift J, Athirasala A, Shin JW, Rehfeldt F, Discher DE. Coordinated increase of nuclear tension and lamin‐A with matrix stiffness outcompetes lamin‐B receptor that favors soft tissue phenotypes. Mol Biol Cell 28: 3333‐3348, 2017.
 55.Buxboim A, Swift J, Irianto J, Spinler KR, Dingal PC, Athirasala A, Kao YR, Cho S, Harada T, Shin JW, Discher DE. Matrix elasticity regulates lamin‐A,C phosphorylation and turnover with feedback to actomyosin. Curr Biol 24: 1909‐1917, 2014.
 56.Caliari SR, Perepelyuk M, Cosgrove BD, Tsai SJ, Lee GY, Mauck RL, Wells RG, Burdick JA. Stiffening hydrogels for investigating the dynamics of hepatic stellate cell mechanotransduction during myofibroblast activation. Sci Rep 6: 21387, 2016.
 57.Cao Y, Lee BH, Peled HB, Venkatraman SS. Synthesis of stiffness‐tunable and cell‐responsive Gelatin‐poly(ethylene glycol) hydrogel for three‐dimensional cell encapsulation. J Biomed Mater Res A 104: 2401‐2411, 2016.
 58.Caplan MR, Schwartzfarb EM, Zhang S, Kamm RD, Lauffenburger DA. Control of self‐assembling oligopeptide matrix formation through systematic variation of amino acid sequence. Biomaterials 23: 219‐227, 2002.
 59.Chai S, Chai Q, Danielsen CC, Hjorth P, Nyengaard JR, Ledet T, Yamaguchi Y, Rasmussen LM, Wogensen L. Overexpression of hyaluronan in the tunica media promotes the development of atherosclerosis. Circ Res 96: 583‐591, 2005.
 60.Chakraborty M, Chu K, Shrestha A, Revelo XS, Zhang X, Gold MJ, Khan S, Lee M, Huang C, Akbari M, Barrow F, Chan YT, Lei H, Kotoulas NK, Jovel J, Pastrello C, Kotlyar M, Goh C, Michelakis E, Clemente‐Casares X, Ohashi PS, Engleman EG, Winer S, Jurisica I, Tsai S, Winer DA. Mechanical stiffness controls dendritic cell metabolism and function. Cell Rep 34: 108609, 2021.
 61.Chan CE, Odde DJ. Traction dynamics of filopodia on compliant substrates. Science 322: 1687‐1691, 2008.
 62.Chao PH, Sheng SC, Chang WR. Micro‐composite substrates for the study of cell‐matrix mechanical interactions. J Mech Behav Biomed Mater 38: 232‐241, 2014.
 63.Chaudhuri O, Cooper‐White J, Janmey PA, Mooney DJ, Shenoy VB. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584: 535‐546, 2020.
 64.Chen H, Qu J, Huang X, Kurundkar A, Zhu L, Yang N, Venado A, Ding Q, Liu G, Antony VB, Thannickal VJ, Zhou Y. Mechanosensing by the α6‐integrin confers an invasive fibroblast phenotype and mediates lung fibrosis. Nat Commun 7: 12564, 2016.
 65.Chen HI, Sudol M. The WW domain of Yes‐associated protein binds a proline‐rich ligand that differs from the consensus established for Src homology 3‐binding modules. Proc Natl Acad Sci U S A 92: 7819‐7823, 1995.
 66.Chen M, Zhang Y, Zhou P, Liu X, Zhao H, Zhou X, Gu Q, Li B, Zhu X, Shi Q. Substrate stiffness modulates bone marrow‐derived macrophage polarization through NF‐kappaB signaling pathway. Bioact Mater 5: 880‐890, 2020.
 67.Chen Y, Terajima M, Yang Y, Sun L, Ahn YH, Pankova D, Puperi DS, Watanabe T, Kim MP, Blackmon SH, Rodriguez J, Liu H, Behrens C, Wistuba II, Minelli R, Scott KL, Sanchez‐Adams J, Guilak F, Pati D, Thilaganathan N, Burns AR, Creighton CJ, Martinez ED, Zal T, Grande‐Allen KJ, Yamauchi M, Kurie JM. Lysyl hydroxylase 2 induces a collagen cross‐link switch in tumor stroma. J Clin Invest 125: 1147‐1162, 2015.
 68.Cheng X, Yang Y, Fan Z, Yu L, Bai H, Zhou B, Wu X, Xu H, Fang M, Shen A, Chen Q, Xu Y. MKL1 potentiates lung cancer cell migration and invasion by epigenetically activating MMP9 transcription. Oncogene 34: 5570‐5581, 2015.
 69.Chien JW, Richards TJ, Gibson KF, Zhang Y, Lindell KO, Shao L, Lyman SK, Adamkewicz JI, Smith V, Kaminski N, O'Riordan T. Serum lysyl oxidase‐like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J 43: 1430‐1438, 2014.
 70.Chin L, Xia Y, Discher DE, Janmey PA. Mechanotransduction in cancer. Curr Opin Chem Eng 11: 77‐84, 2016.
 71.Choi CM, Jang SJ, Park SY, Choi YB, Jeong JH, Kim DS, Kim HK, Park KS, Nam BH, Kim HR, Kim SY, Hong KM, KTORG. Transglutaminase 2 as an independent prognostic marker for survival of patients with non‐adenocarcinoma subtype of non‐small cell lung cancer. Mol Cancer 10: 119, 2011.
 72.Chopra A, Lin V, McCollough A, Atzet S, Prestwich GD, Wechsler AS, Murray ME, Oake SA, Kresh JY, Janmey PA. Reprogramming cardiomyocyte mechanosensing by crosstalk between integrins and hyaluronic acid receptors. J Biomech 45: 824‐831, 2012.
 73.Chowdhury F, Li Y, Poh YC, Yokohama‐Tamaki T, Wang N, Tanaka TS. Soft substrates promote homogeneous self‐renewal of embryonic stem cells via downregulating cell‐matrix tractions. PLoS One 5: e15655, 2010.
 74.Clevers H. Modeling development and disease with organoids. Cell 165: 1586‐1597, 2016.
 75.Codelia VA, Sun G, Irvine KD. Regulation of YAP by mechanical strain through Jnk and Hippo signaling. Curr Biol 24: 2012‐2017, 2014.
 76.Collum SD, Chen NY, Hernandez AM, Hanmandlu A, Sweeney H, Mertens TCJ, Weng T, Luo F, Molina JG, Davies J, Horan IP, Morrell NW, Amione‐Guerra J, Al‐Jabbari O, Youker K, Sun W, Rajadas J, Bollyky PL, Akkanti BH, Jyothula S, Sinha N, Guha A, Karmouty‐Quintana H. Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis. Br J Pharmacol 174: 3284‐3301, 2017.
 77.Corsi A, Xu T, Chen XD, Boyde A, Liang J, Mankani M, Sommer B, Iozzo RV, Eichstetter I, Robey PG, Bianco P, Young MF. Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers‐Danlos‐like changes in bone and other connective tissues. J Bone Miner Res 17: 1180‐1189, 2002.
 78.Cortiella J, Niles J, Cantu A, Brettler A, Pham A, Vargas G, Winston S, Wang J, Walls S, Nichols JE. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. Tissue Eng Part A 16: 2565‐2580, 2010.
 79.Costell M, Gustafsson E, Aszódi A, Mörgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fässler R. Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol 147: 1109‐1122, 1999.
 80.Crest J, Diz‐Muñoz A, Chen DY, Fletcher DA, Bilder D. Organ sculpting by patterned extracellular matrix stiffness. Elife 6: e24958, 2017.
 81.Cretu A, Castagnino P, Assoian R. Studying the effects of matrix stiffness on cellular function using acrylamide‐based hydrogels. J Vis Exp, 2010.
 82.Cui Y, Hameed FM, Yang B, Lee K, Pan CQ, Park S, Sheetz M. Cyclic stretching of soft substrates induces spreading and growth. Nat Commun 6: 6333, 2015.
 83.Damljanović V, Lagerholm BC, Jacobson K. Bulk and micropatterned conjugation of extracellular matrix proteins to characterized polyacrylamide substrates for cell mechanotransduction assays. Biotechniques 39: 847‐851, 2005.
 84.Das RK, Gocheva V, Hammink R, Zouani OF, Rowan AE. Stress‐stiffening‐mediated stem‐cell commitment switch in soft responsive hydrogels. Nat Mater 15: 318‐325, 2016. Hilster RHJ, Sharma PK, Jonker MR, White ES, Gercama EA, Roobeek M, Timens W, Harmsen MC, Hylkema MN, Burgess JK. Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue. Am J Physiol Lung Cell Mol Physiol 318: L698‐L704, 2020. la Zerda A, Kratochvil MJ, Suhar NA, Heilshorn SC. Review: Bioengineering strategies to probe T cell mechanobiology. APL Bioeng 2: 021501, 2018.
 87.De Langhe SP, Sala FG, Del Moral PM, Fairbanks TJ, Yamada KM, Warburton D, Burns RC, Bellusci S. Dickkopf‐1 (DKK1) reveals that fibronectin is a major target of Wnt signaling in branching morphogenesis of the mouse embryonic lung. Dev Biol 277: 316‐331, 2005.
 88.Degos F, Perez P, Roche B, Mahmoudi A, Asselineau J, Voitot H, Bedossa P, Group Fs. Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study). J Hepatol 53: 1013‐1021, 2010.
 89.del Rio A, Perez‐Jimenez R, Liu R, Roca‐Cusachs P, Fernandez JM, Sheetz MP. Stretching single talin rod molecules activates vinculin binding. Science 323: 638‐641, 2009.
 90.Deng CX, Hong X, Stegemann JP. Ultrasound imaging techniques for spatiotemporal characterization of composition, microstructure, and mechanical properties in tissue engineering. Tissue Eng Part B Rev 22: 311‐321, 2016.
 91.Deng M, Lin J, Nowsheen S, Liu T, Zhao Y, Villalta PW, Sicard D, Tschumperlin DJ, Lee S, Kim J, Lou Z. Extracellular matrix stiffness determines DNA repair efficiency and cellular sensitivity to genotoxic agents. Sci Adv 6: eabb2630, 2020.
 92.Dewall RJ. Ultrasound elastography: Principles, techniques, and clinical applications. Crit Rev Biomed Eng 41: 1‐19, 2013.
 93.Dieffenbach PB, Haeger CM, Coronata AMF, Choi KM, Varelas X, Tschumperlin DJ, Fredenburgh LE. Arterial stiffness induces remodeling phenotypes in pulmonary artery smooth muscle cells via YAP/TAZ‐mediated repression of cyclooxygenase‐2. Am J Physiol Lung Cell Mol Physiol 313: L628‐L647, 2017.
 94.Dingal PC, Bradshaw AM, Cho S, Raab M, Buxboim A, Swift J, Discher DE. Fractal heterogeneity in minimal matrix models of scars modulates stiff‐niche stem‐cell responses via nuclear exit of a mechanorepressor. Nat Mater 14: 951‐960, 2015.
 95.Discher DE, Janmey P, Wang YL. Tissue cells feel and respond to the stiffness of their substrate. Science 310: 1139‐1143, 2005.
 96.Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science 324: 1673‐1677, 2009.
 97.Doherty JR, Trahey GE, Nightingale KR, Palmeri ML. Acoustic radiation force elasticity imaging in diagnostic ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control 60: 685‐701, 2013.
 98.Dong B, Hannezo E, Hayashi S. Balance between apical membrane growth and luminal matrix resistance determines epithelial tubule shape. Cell Rep 7: 941‐950, 2014.
 99.Du J, Zu Y, Li J, Du S, Xu Y, Zhang L, Jiang L, Wang Z, Chien S, Yang C. Extracellular matrix stiffness dictates Wnt expression through integrin pathway. Sci Rep 6: 20395, 2016.
 100.Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Satchell L, Kumar A, Pathmanathan L, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ. Decorin expression is important for age‐related changes in tendon structure and mechanical properties. Matrix Biol 32: 3‐13, 2013.
 101.Dunphy SE, Bratt JA, Akram KM, Forsyth NR, El Haj AJ. Hydrogels for lung tissue engineering: Biomechanical properties of thin collagen‐elastin constructs. J Mech Behav Biomed Mater 38: 251‐259, 2014.
 102.Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, Elvassore N, Piccolo S. Role of YAP/TAZ in mechanotransduction. Nature 474: 179‐183, 2011.
 103.Ebihara T, Venkatesan N, Tanaka R, Ludwig MS. Changes in extracellular matrix and tissue viscoelasticity in bleomycin‐induced lung fibrosis. Temporal aspects. Am J Respir Crit Care Med 162: 1569‐1576, 2000.
 104.Eekhoff JD, Fang F, Lake SP. Multiscale mechanical effects of native collagen cross‐linking in tendon. Connect Tissue Res 59: 410‐422, 2018.
 105.Ehrlich SF, Quesenberry CP, Van Den Eeden SK, Shan J, Ferrara A. Patients diagnosed with diabetes are at increased risk for asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and pneumonia but not lung cancer. Diabetes Care 33: 55‐60, 2010.
 106.Eisenberg JL, Safi A, Wei X, Espinosa HD, Budinger GS, Takawira D, Hopkinson SB, Jones JC. Substrate stiffness regulates extracellular matrix deposition by alveolar epithelial cells. Res Rep Biol 1–12: 2011, 2011.
 107.Elosegui‐Artola A. The extracellular matrix viscoelasticity as a regulator of cell and tissue dynamics. Curr Opin Cell Biol 72: 10‐18, 2021.
 108.Elosegui‐Artola A, Bazellières E, Allen MD, Andreu I, Oria R, Sunyer R, Gomm JJ, Marshall JF, Jones JL, Trepat X, Roca‐Cusachs P. Rigidity sensing and adaptation through regulation of integrin types. Nat Mater 13: 631‐637, 2014.
 109.Eng D, Caplan M, Preul M, Panitch A. Hyaluronan scaffolds: A balance between backbone functionalization and bioactivity. Acta Biomater 6: 2407‐2414, 2010.
 110.Engler A, Bacakova L, Newman C, Hategan A, Griffin M, Discher D. Substrate compliance versus ligand density in cell on gel responses. Biophys J 86: 617‐628, 2004.
 111.Engler AJ, Rehfeldt F, Sen S, Discher DE. Microtissue elasticity: Measurements by atomic force microscopy and its influence on cell differentiation. Methods Cell Biol 83: 521‐545, 2007.
 112.Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell 126: 677‐689, 2006.
 113.Enomoto T, Usuki J, Azuma A, Nakagawa T, Kudoh S. Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis. Chest 123: 2007‐2011, 2003.
 114.Evans ND, Minelli C, Gentleman E, LaPointe V, Patankar SN, Kallivretaki M, Chen X, Roberts CJ, Stevens MM. Substrate stiffness affects early differentiation events in embryonic stem cells. Eur Cell Mater 18: 1‐13; discussion 13‐14, 2009.
 115.Fairbanks BD, Schwartz MP, Halevi AE, Nuttelman CR, Bowman CN, Anseth KS. A versatile synthetic extracellular matrix mimic via thiol‐norbornene photopolymerization. Adv Mater 21: 5005‐5010, 2009.
 116.Feng J, Tang Y, Xu Y, Sun Q, Liao F, Han D. Substrate stiffness influences the outcome of antitumor drug screening in vitro. Clin Hemorheol Microcirc 55: 121‐131, 2013.
 117.Feng X, Degese MS, Iglesias‐Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, Zaidi MR, Ksander BR, Merlino G, Sodhi A, Chen Q, Gutkind JS. Hippo‐independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio‐regulated rho GTPase signaling circuitry. Cancer Cell 25: 831‐845, 2014.
 118.Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch D, Groshong S, Collard HR, Wolters PJ, Bradford WZ, Kossen K, Seiwert SD, du Bois RM, Garcia CK, Devine MS, Gudmundsson G, Isaksson HJ, Kaminski N, Zhang Y, Gibson KF, Lancaster LH, Cogan JD, Mason WR, Maher TM, Molyneaux PL, Wells AU, Moffatt MF, Selman M, Pardo A, Kim DS, Crapo JD, Make BJ, Regan EA, Walek DS, Daniel JJ, Kamatani Y, Zelenika D, Smith K, McKean D, Pedersen BS, Talbert J, Kidd RN, Markin CR, Beckman KB, Lathrop M, Schwarz MI, Schwartz DA. Genome‐wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet 45: 613‐620, 2013.
 119.Fiore VF, Strane PW, Bryksin AV, White ES, Hagood JS, Barker TH. Conformational coupling of integrin and Thy‐1 regulates Fyn priming and fibroblast mechanotransduction. J Cell Biol 211: 173‐190, 2015.
 120.Fiore VF, Wong SS, Tran C, Tan C, Xu W, Sulchek T, White ES, Hagood JS, Barker TH. αvβ3 Integrin drives fibroblast contraction and strain stiffening of soft provisional matrix during progressive fibrosis. JCI Insight 3 (20): 3, e97597, 2018.
 121.Fischer RS, Gardel M, Ma X, Adelstein RS, Waterman CM. Local cortical tension by myosin II guides 3D endothelial cell branching. Curr Biol 19: 260‐265, 2009.
 122.Forget A, Christensen J, Lüdeke S, Kohler E, Tobias S, Matloubi M, Thomann R, Shastri VP. Polysaccharide hydrogels with tunable stiffness and provasculogenic properties via α‐helix to β‐sheet switch in secondary structure. Proc Natl Acad Sci U S A 110: 12887‐12892, 2013.
 123.Fortunati D, Chau DY, Wang Z, Collighan RJ, Griffin M. Cross‐linking of collagen I by tissue transglutaminase provides a promising biomaterial for promoting bone healing. Amino Acids 46: 1751‐1761, 2014.
 124.Frey MT, Engler A, Discher DE, Lee J, Wang YL. Microscopic methods for measuring the elasticity of gel substrates for cell culture: Microspheres, microindenters, and atomic force microscopy. Methods Cell Biol 83: 47‐65, 2007.
 125.Frey MT, Wang YL. A photo‐modulatable material for probing cellular responses to substrate rigidity. Soft Matter 5: 1918‐1924, 2009.
 126.Friedman SL, Sheppard D, Duffield JS, Violette S. Therapy for fibrotic diseases: Nearing the starting line. Sci Transl Med 5: 167sr161, 2013.
 127.Fu J, Wang YK, Yang MT, Desai RA, Yu X, Liu Z, Chen CS. Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat Methods 7: 733‐736, 2010.
 128.Fukui L, Henry JJ. FGF signaling is required for lens regeneration in Xenopus laevis. Biol Bull 221: 137‐145, 2011.
 129.Gan CT, Lankhaar JW, Westerhof N, Marcus JT, Becker A, Twisk JW, Boonstra A, Postmus PE, Vonk‐Noordegraaf A. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest 132: 1906‐1912, 2007.
 130.García‐Sancho Figueroa MC, Carrillo G, Pérez‐Padilla R, Fernández‐Plata MR, Buendía‐Roldán I, Vargas MH, Selman M. Risk factors for idiopathic pulmonary fibrosis in a Mexican population. A case‐control study. Respir Med 104: 305‐309, 2010.
 131.Geerligs M, Peters GW, Ackermans PA, Oomens CW, Baaijens FP. Linear viscoelastic behavior of subcutaneous adipose tissue. Biorheology 45: 677‐688, 2008.
 132.Ghajar CM, Chen X, Harris JW, Suresh V, Hughes CC, Jeon NL, Putnam AJ, George SC. The effect of matrix density on the regulation of 3‐D capillary morphogenesis. Biophys J 94: 1930‐1941, 2008.
 133.Giacomini MM, Travis MA, Kudo M, Sheppard D. Epithelial cells utilize cortical actin/myosin to activate latent TGF‐β through integrin α(v)β(6)‐dependent physical force. Exp Cell Res 318: 716‐722, 2012.
 134.Gilbert PM, Havenstrite KL, Magnusson KE, Sacco A, Leonardi NA, Kraft P, Nguyen NK, Thrun S, Lutolf MP, Blau HM. Substrate elasticity regulates skeletal muscle stem cell self‐renewal in culture. Science 329: 1078‐1081, 2010.
 135.Glaser KJ, Manduca A, Ehman RL. Review of MR elastography applications and recent developments. J Magn Reson Imaging 36: 757‐774, 2012.
 136.Gould ST, Darling NJ, Anseth KS. Small peptide functionalized thiol‐ene hydrogels as culture substrates for understanding valvular interstitial cell activation and de novo tissue deposition. Acta Biomater 8: 3201‐3209, 2012.
 137.Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466: 263‐266, 2010.
 138.Grevesse T, Versaevel M, Circelli G, Desprez S, Gabriele S. A simple route to functionalize polyacrylamide hydrogels for the independent tuning of mechanotransduction cues. Lab Chip 13: 777‐780, 2013.
 139.Grevesse T, Versaevel M, Gabriele S. Preparation of hydroxy‐PAAm hydrogels for decoupling the effects of mechanotransduction cues. J Vis Exp, 2014.
 140.Gribbin J, Hubbard R, Smith C. Role of diabetes mellitus and gastro‐oesophageal reflux in the aetiology of idiopathic pulmonary fibrosis. Respir Med 103: 927‐931, 2009.
 141.Griffin M, Casadio R, Bergamini CM. Transglutaminases: Nature's biological glues. Biochem J 368: 377‐396, 2002.
 142.Grosskopf AK, Truby RL, Kim H, Perazzo A, Lewis JA, Stone HA. Viscoplastic matrix materials for embedded 3D printing. ACS Appl Mater Interfaces 10: 23353‐23361, 2018.
 143.Gu Z, Liu F, Tonkova EA, Lee SY, Tschumperlin DJ, Brenner MB. Soft matrix is a natural stimulator for cellular invasiveness. Mol Biol Cell, 2013.
 144.Gundy S, Manning G, O'Connell E, Ellä V, Harwoko MS, Rochev Y, Smith T, Barron V. Human coronary artery smooth muscle cell response to a novel PLA textile/fibrin gel composite scaffold. Acta Biomater 4: 1734‐1744, 2008.
 145.Guo L, Cui C, Zhang K, Wang J, Wang Y, Lu Y, Chen K, Yuan J, Xiao G, Tang B, Sun Y, Wu C. Kindlin‐2 links mechano‐environment to proline synthesis and tumor growth. Nat Commun 10: 845, 2019.
 146.Gupta M, Doss B, Lim CT, Voituriez R, Ladoux B. Single cell rigidity sensing: A complex relationship between focal adhesion dynamics and large‐scale actin cytoskeleton remodeling. Cell Adh Migr 10: 554‐567, 2016.
 147.Gutierrez E, Tkachenko E, Besser A, Sundd P, Ley K, Danuser G, Ginsberg MH, Groisman A. High refractive index silicone gels for simultaneous total internal reflection fluorescence and traction force microscopy of adherent cells. PLoS One 6: e23807, 2011.
 148.Guvendiren M, Burdick JA. Stiffening hydrogels to probe short‐ and long‐term cellular responses to dynamic mechanics. Nat Commun 3: 792, 2012.
 149.Guvendiren M, Perepelyuk M, Wells RG, Burdick JA. Hydrogels with differential and patterned mechanics to study stiffness‐mediated myofibroblastic differentiation of hepatic stellate cells. J Mech Behav Biomed Mater 38: 198‐208, 2014.
 150.Haak AJ, Kostallari E, Sicard D, Ligresti G, Choi KM, Caporarello N, Jones DL, Tan Q, Meridew J, Diaz Espinosa AM, Aravamudhan A, Maiers JL, Britt RD, Roden AC, Pabelick CM, Prakash YS, Nouraie SM, Li X, Zhang Y, Kass DJ, Lagares D, Tager AM, Varelas X, Shah VH, Tschumperlin DJ. Selective YAP/TAZ inhibition in fibroblasts via dopamine receptor D1 agonism reverses fibrosis. Sci Transl Med 11, 2019.
 151.Hadden WJ, Young JL, Holle AW, McFetridge ML, Kim DY, Wijesinghe P, Taylor‐Weiner H, Wen JH, Lee AR, Bieback K, Vo BN, Sampson DD, Kennedy BF, Spatz JP, Engler AJ, Choi YS. Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels. Proc Natl Acad Sci U S A 114: 5647‐5652, 2017.
 152.Han YL, Ronceray P, Xu G, Malandrino A, Kamm RD, Lenz M, Broedersz CP, Guo M. Cell contraction induces long‐ranged stress stiffening in the extracellular matrix. Proc Natl Acad Sci U S A 115: 4075‐4080, 2018.
 153.Hansen ML, Rasmussen LM. Associations between plasma fibulin‐1, pulse wave velocity and diabetes in patients with coronary heart disease. J Diabetes Complications 29: 362‐366, 2015.
 154.Harada T, Swift J, Irianto J, Shin JW, Spinler KR, Athirasala A, Diegmiller R, Dingal PC, Ivanovska IL, Discher DE. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J Cell Biol 204: 669‐682, 2014.
 155.Hayashi S, Dong B. Shape and geometry control of the Drosophila tracheal tubule. Dev Growth Differ 59: 4‐11, 2017.
 156.Hecker L, Logsdon NJ, Kurundkar D, Kurundkar A, Bernard K, Hock T, Meldrum E, Sanders YY, Thannickal VJ. Reversal of persistent fibrosis in aging by targeting Nox4‐Nrf2 redox imbalance. Sci Transl Med 6: 231ra247, 2014.
 157.Henderson NC, Arnold TD, Katamura Y, Giacomini MM, Rodriguez JD, McCarty JH, Pellicoro A, Raschperger E, Betsholtz C, Ruminski PG, Griggs DW, Prinsen MJ, Maher JJ, Iredale JP, Lacy‐Hulbert A, Adams RH, Sheppard D. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med 19: 1617‐1624, 2013.
 158.Herrera J, Henke CA, Bitterman PB. Extracellular matrix as a driver of progressive fibrosis. J Clin Invest 128: 45‐53, 2018.
 159.Hickey JW, Dong Y, Chung JW, Salathe SF, Pruitt HC, Li X, Chang C, Fraser AK, Bessell CA, Ewald AJ, Gerecht S, Mao HQ, Schneck JP. Engineering an artificial T‐cell stimulating matrix for immunotherapy. Adv Mater 31: e1807359, 2019.
 160.Higuchi S, Watanabe TM, Kawauchi K, Ichimura T, Fujita H. Culturing of mouse and human cells on soft substrates promote the expression of stem cell markers. J Biosci Bioeng 117: 749‐755, 2014.
 161.Hind LE, Dembo M, Hammer DA. Macrophage motility is driven by frontal‐towing with a force magnitude dependent on substrate stiffness. Integr Biol (Camb) 7: 447‐453, 2015.
 162.Hinz B, Gabbiani G, Chaponnier C. The NH2‐terminal peptide of alpha‐smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo. J Cell Biol 157: 657‐663, 2002.
 163.Hinz B, Phan SH, Thannickal VJ, Prunotto M, Desmouliere A, Varga J, De Wever O, Mareel M, Gabbiani G. Recent developments in myofibroblast biology: Paradigms for connective tissue remodeling. Am J Pathol, 2012.
 164.Hobbs BD, de Jong K, Lamontagne M, Bossé Y, Shrine N, Artigas MS, Wain LV, Hall IP, Jackson VE, Wyss AB, London SJ, North KE, Franceschini N, Strachan DP, Beaty TH, Hokanson JE, Crapo JD, Castaldi PJ, Chase RP, Bartz TM, Heckbert SR, Psaty BM, Gharib SA, Zanen P, Lammers JW, Oudkerk M, Groen HJ, Locantore N, Tal‐Singer R, Rennard SI, Vestbo J, Timens W, Paré PD, Latourelle JC, Dupuis J, O'Connor GT, Wilk JB, Kim WJ, Lee MK, Oh YM, Vonk JM, de Koning HJ, Leng S, Belinsky SA, Tesfaigzi Y, Manichaikul A, Wang XQ, Rich SS, Barr RG, Sparrow D, Litonjua AA, Bakke P, Gulsvik A, Lahousse L, Brusselle GG, Stricker BH, Uitterlinden AG, Ampleford EJ, Bleecker ER, Woodruff PG, Meyers DA, Qiao D, Lomas DA, Yim JJ, Kim DK, Hawrylkiewicz I, Sliwinski P, Hardin M, Fingerlin TE, Schwartz DA, Postma DS, MacNee W, Tobin MD, Silverman EK, Boezen HM, Cho MH, Investigators C, Investigators E, Investigators L, Group SR, Investigators ICGN, Investigators UB, and Consortium ICG. Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis. Nat Genet 49: 426‐432, 2017.
 165.Hoffman BD, Grashoff C, Schwartz MA. Dynamic molecular processes mediate cellular mechanotransduction. Nature 475: 316‐323, 2011.
 166.Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 4: 435‐459, 2009.
 167.Horowitz JC, Tschumperlin DJ, Kim KK, Osterholzer JJ, Subbotina N, Ajayi IO, Teitz‐Tennenbaum S, Virk A, Dotson M, Liu F, Sicard D, Jia S, Sisson TH. Urokinase plasminogen activator overexpression reverses established lung fibrosis. Thromb Haemost 119: 1968‐1980, 2019.
 168.Hsu SJ, Bouchard RR, Dumont DM, Wolf PD, Trahey GE. In vivo assessment of myocardial stiffness with acoustic radiation force impulse imaging. Ultrasound Med Biol 33: 1706‐1719, 2007.
 169.Huang K, Mitzner W, Rabold R, Schofield B, Lee H, Biswal S, Tankersley CG. Variation in senescent‐dependent lung changes in inbred mouse strains. J Appl Physiol 102 (1632‐1639): 2007, 1985.
 170.Huang X, Yang N, Fiore VF, Barker TH, Sun Y, Morris SW, Ding Q, Thannickal VJ, Zhou Y. Matrix stiffness‐induced myofibroblast differentiation is mediated by intrinsic mechanotransduction. Am J Respir Cell Mol Biol 47: 340‐348, 2012.
 171.Huebsch N, Arany PR, Mao AS, Shvartsman D, Ali OA, Bencherif SA, Rivera‐Feliciano J, Mooney DJ. Harnessing traction‐mediated manipulation of the cell/matrix interface to control stem‐cell fate. Nat Mater 9: 518‐526, 2010.
 172.Hunter KS, Lammers SR, Shandas R. Pulmonary vascular stiffness: Measurement, modeling, and implications in normal and hypertensive pulmonary circulations. Compr Physiol 1: 1413‐1435, 2011.
 173.Huse M. Mechanical forces in the immune system. Nat Rev Immunol 17: 679‐690, 2017.
 174.Hynes RO. Stretching the boundaries of extracellular matrix research. Nat Rev Mol Cell Biol 15: 761‐763, 2014.
 175.Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K, Pollok K, Ferkowicz MJ, Gilley D, Yoder MC. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 104: 2752‐2760, 2004.
 176.Isenberg BC, Dimilla PA, Walker M, Kim S, Wong JY. Vascular smooth muscle cell durotaxis depends on substrate stiffness gradient strength. Biophys J 97: 1313‐1322, 2009.
 177.Ishihara S, Yasuda M, Harada I, Mizutani T, Kawabata K, Haga H. Substrate stiffness regulates temporary NF‐κB activation via actomyosin contractions. Exp Cell Res 319: 2916‐2927, 2013.
 178.Issa R, Zhou X, Constandinou CM, Fallowfield J, Millward‐Sadler H, Gaca MD, Sands E, Suliman I, Trim N, Knorr A, Arthur MJ, Benyon RC, Iredale JP. Spontaneous recovery from micronodular cirrhosis: Evidence for incomplete resolution associated with matrix cross‐linking. Gastroenterology 126: 1795‐1808, 2004.
 179.Ito S, Ingenito EP, Brewer KK, Black LD, Parameswaran H, Lutchen KR, Suki B. Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: Possible role of collagen remodeling. J Appl Physiol 98 (503‐511): 2005, 1985.
 180.Iwasaki A, Sakai K, Moriya K, Sasaki T, Keene DR, Akhtar R, Miyazono T, Yasumura S, Watanabe M, Morishita S, Sakai T. Molecular mechanism responsible for fibronectin‐controlled alterations in matrix stiffness in advanced chronic liver fibrogenesis. J Biol Chem 291: 72‐88, 2016.
 181.Jacks T, Weinberg RA. Taking the study of cancer cell survival to a new dimension. Cell 111: 923‐925, 2002.
 182.Jamieson RR, Stasiak SE, Polio SR, Augspurg RD, McCormick CA, Ruberti JW, Parameswaran H. Stiffening of the extracellular matrix is a sufficient condition for airway hyperreactivity. J Appl Physiol 130 (1635‐1645): 2021, 1985.
 183.Jang J, Kim TG, Kim BS, Kim SW, Kwon SM, Cho DW. Tailoring mechanical properties of decellularized extracellular matrix bioink by vitamin B2‐induced photo‐crosslinking. Acta Biomater 33: 88‐95, 2016.
 184.Jaspers M, Dennison M, Mabesoone MF, MacKintosh FC, Rowan AE, Kouwer PH. Ultra‐responsive soft matter from strain‐stiffening hydrogels. Nat Commun 5: 5808, 2014.
 185.Jaspers M, Pape AC, Voets IK, Rowan AE, Portale G, Kouwer PH. Bundle formation in biomimetic hydrogels. Biomacromolecules 17: 2642‐2649, 2016.
 186.Jaspers M, Vaessen SL, van Schayik P, Voerman D, Rowan AE, Kouwer PHJ. Nonlinear mechanics of hybrid polymer networks that mimic the complex mechanical environment of cells. Nat Commun 8: 15478, 2017.
 187.Jeong J, Keum S, Kim D, You E, Ko P, Lee J, Kim J, Kim J‐W, Rhee S. Spindle pole body component 25 homolog expressed by ECM stiffening is required for lung cancer cell proliferation. Biochem Biophys Res Commun 500: 937‐943, 2018.
 188.Jiang S, Lyu C, Zhao P, Li W, Kong W, Huang C, Genin GM, Du Y. Cryoprotectant enables structural control of porous scaffolds for exploration of cellular mechano‐responsiveness in 3D. Nat Commun 10: 3491, 2019.
 189.Jones DL, Meridew JA, Link PA, Ducharme MT, Lydon KL, Choi KM, Caporarello N, Tan Q, Diaz Espinosa AM, Xiong Y, Lee JH, Ye Z, Yan H, Ordog T, Ligresti G, Varelas X, Tschumperlin DJ. ZNF416 is a pivotal transcriptional regulator of fibroblast mechanoactivation. J Cell Biol 220, 2021.
 190.Jones MG, Andriotis OG, Roberts JJ, Lunn K, Tear VJ, Cao L, Ask K, Smart DE, Bonfanti A, Johnson P, Alzetani A, Conforti F, Doherty R, Lai CY, Johnson B, Bourdakos KN, Fletcher SV, Marshall BG, Jogai S, Brereton CJ, Chee SJ, Ottensmeier CH, Sime P, Gauldie J, Kolb M, Mahajan S, Fabre A, Bhaskar A, Jarolimek W, Richeldi L, O'Reilly KM, Monk PD, Thurner PJ, Davies DE. Nanoscale dysregulation of collagen structure‐function disrupts mechano‐homeostasis and mediates pulmonary fibrosis. Elife 7, 2018.
 191.Jorba I, Uriarte JJ, Campillo N, Farré R, Navajas D. Probing micromechanical properties of the extracellular matrix of soft tissues by atomic force microscopy. J Cell Physiol 232: 19‐26, 2017.
 192.Judokusumo E, Tabdanov E, Kumari S, Dustin ML, Kam LC. Mechanosensing in T lymphocyte activation. Biophys J 102: L5‐L7, 2012.
 193.Kadler KE, Baldock C, Bella J, Boot‐Handford RP. Collagens at a glance. J Cell Sci 120: 1955‐1958, 2007.
 194.Kalluri R, Weinberg RA. The basics of epithelial‐mesenchymal transition. J Clin Investigat 119: 1420‐1428, 2009.
 195.Kandow CE, Georges PC, Janmey PA, Beningo KA. Polyacrylamide hydrogels for cell mechanics: Steps toward optimization and alternative uses. Methods Cell Biol 83: 29‐46, 2007.
 196.Kapetanaki MG, Mora AL, Rojas M. Influence of age on wound healing and fibrosis. J Pathol 229: 310‐322, 2013.
 197.Karki P, Birukova AA. Substrate stiffness‐dependent exacerbation of endothelial permeability and inflammation: Mechanisms and potential implications in ALI and PH (2017 Grover Conference Series). Pulm Circ 8: 2045894018773044, 2018.
 198.Keating M, Kurup A, Alvarez‐Elizondo M, Levine AJ, Botvinick E. Spatial distributions of pericellular stiffness in natural extracellular matrices are dependent on cell‐mediated proteolysis and contractility. Acta Biomater 57: 304‐312, 2017.
 199.Khatiwala CB, Peyton SR, Putnam AJ. Intrinsic mechanical properties of the extracellular matrix affect the behavior of pre‐osteoblastic MC3T3‐E1 cells. Am J Physiol Cell Physiol 290: C1640‐C1650, 2006.
 200.Khunmanee S, Jeong Y, Park H. Crosslinking method of hyaluronic‐based hydrogel for biomedical applications. J Tissue Eng 8: 2041731417726464, 2017.
 201.Kim D, You E, Jeong J, Ko P, Kim JW, Rhee S. DDR2 controls the epithelial‐mesenchymal‐transition‐related gene expression via c‐Myb acetylation upon matrix stiffening. Sci Rep 7: 6847, 2017.
 202.Kim YJ, Park JW, Kyung SY, Lee SP, Chung MP, Kim YH, Lee JH, Kim YC, Ryu JS, Lee HL, Park CS, Uh ST, Lee YC, Kim KH, Chun YJ, Park YB, Kim DS, Jegal Y, Park MS, Jeong SH. Clinical characteristics of idiopathic pulmonary fibrosis patients with diabetes mellitus: The national survey in Korea from 2003 to 2007. J Korean Med Sci 27: 756‐760, 2012.
 203.Klingberg F, Chow ML, Koehler A, Boo S, Buscemi L, Quinn TM, Costell M, Alman BA, Genot E, Hinz B. Prestress in the extracellular matrix sensitizes latent TGF‐β1 for activation. J Cell Biol 207: 283‐297, 2014.
 204.Kloxin AM, Kasko AM, Salinas CN, Anseth KS. Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324: 59‐63, 2009.
 205.Kocgozlu L, Lavalle P, Koenig G, Senger B, Haikel Y, Schaaf P, Voegel JC, Tenenbaum H, Vautier D. Selective and uncoupled role of substrate elasticity in the regulation of replication and transcription in epithelial cells. J Cell Sci 123: 29‐39, 2010.
 206.Kouwer PH, Koepf M, Le Sage VA, Jaspers M, van Buul AM, Eksteen‐Akeroyd ZH, Woltinge T, Schwartz E, Kitto HJ, Hoogenboom R, Picken SJ, Nolte RJ, Mendes E, Rowan AE. Responsive biomimetic networks from polyisocyanopeptide hydrogels. Nature 493: 651‐655, 2013.
 207.Kumar A, Placone JK, Engler AJ. Understanding the extracellular forces that determine cell fate and maintenance. Development 144: 4261‐4270, 2017.
 208.Kyung SY, Byun KH, Yoon JY, Kim YJ, Lee SP, Park JW, Lee BH, Park JS, Jang AS, Park CS, Jeong SH. Advanced glycation end‐products and receptor for advanced glycation end‐products expression in patients with idiopathic pulmonary fibrosis and NSIP. Int J Clin Exp Pathol 7: 221‐228, 2014.
 209.Lammers SR, Kao PH, Qi HJ, Hunter K, Lanning C, Albietz J, Hofmeister S, Mecham R, Stenmark KR, Shandas R. Changes in the structure‐function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves. Am J Physiol Heart Circ Physiol 295: H1451‐H1459, 2008.
 210.Lang MR, Fiaux GW, Gillooly M, Stewart JA, Hulmes DJ, Lamb D. Collagen content of alveolar wall tissue in emphysematous and non‐emphysematous lungs. Thorax 49: 319‐326, 1994.
 211.Lee D, Rahman MM, Zhou Y, Ryu S. Three‐dimensional confocal microscopy indentation method for hydrogel elasticity measurement. Langmuir 31: 9684‐9693, 2015.
 212.Lee JY, Oh JG, Kim JS, Lee KW. Effects of chebulic acid on advanced glycation endproducts‐induced collagen cross‐links. Biol Pharm Bull 37: 1162‐1167, 2014.
 213.Lee KY, Mooney DJ. Alginate: Properties and biomedical applications. Prog Polym Sci 37: 106‐126, 2012.
 214.Leiphart RJ, Chen D, Peredo AP, Loneker AE, Janmey PA. Mechanosensing at cellular interfaces. Langmuir 35: 7509‐7519, 2019.
 215.Lepetit H, Eddahibi S, Fadel E, Frisdal E, Munaut C, Noel A, Humbert M, Adnot S, D'Ortho MP, Lafuma C. Smooth muscle cell matrix metalloproteinases in idiopathic pulmonary arterial hypertension. Eur Respir J 25: 834‐842, 2005.
 216.Li L, Sharma N, Chippada U, Jiang X, Schloss R, Yarmush ML, Langrana NA. Functional modulation of ES‐derived hepatocyte lineage cells via substrate compliance alteration. Ann Biomed Eng 36: 865‐876, 2008.
 217.Liang Y, Walczak P, Bulte JW. The survival of engrafted neural stem cells within hyaluronic acid hydrogels. Biomaterials 34: 5521‐5529, 2013.
 218.Ligresti G, Caporarello N, Meridew JA, Jones DL, Tan Q, Choi KM, Haak AJ, Aravamudhan A, Roden AC, Prakash YS, Lomberk G, Urrutia RA, Tschumperlin DJ. CBX5/G9a/H3K9me‐mediated gene repression is essential to fibroblast activation during lung fibrosis. JCI Insight 5: e127111, 2019.
 219.Lima MJ, Correlo VM, Reis RL. Micro/nano replication and 3D assembling techniques for scaffold fabrication. Mater Sci Eng C Mater Biol Appl 42: 615‐621, 2014.
 220.Lin DC, Yurke B, Langrana NA. Mechanical properties of a reversible, DNA‐crosslinked polyacrylamide hydrogel. J Biomech Eng 126: 104‐110, 2004.
 221.Lin YC, Sung YK, Jiang X, Peters‐Golden M, Nicolls MR. Simultaneously targeting myofibroblast contractility and extracellular matrix cross‐linking as a therapeutic concept in airway fibrosis. Am J Transplant 17: 1229‐1241, 2017.
 222.Link PA, Pouliot RA, Mikhaiel NS, Young BM, Heise RL. Tunable hydrogels from pulmonary extracellular matrix for 3D cell culture. J Vis Exp, 2017.
 223.Liu CY, Chan SW, Guo F, Toloczko A, Cui L, Hong W. MRTF/SRF dependent transcriptional regulation of TAZ in breast cancer cells. Oncotarget 7: 13706‐13716, 2016.
 224.Liu F, Haeger CM, Dieffenbach PB, Sicard D, Chrobak I, Coronata AM, Suárez Velandia MM, Vitali S, Colas RA, Norris PC, Marinković A, Liu X, Ma J, Rose CD, Lee SJ, Comhair SA, Erzurum SC, JD MD, Serhan CN, Walsh SR, Tschumperlin DJ, Fredenburgh LE. Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension. JCI Insight 1: e86987, 2016.
 225.Liu F, Lagares D, Choi KM, Stopfer L, Marinković A, Vrbanac V, Probst CK, Hiemer SE, Sisson TH, Horowitz JC, Rosas IO, Fredenburgh LE, Feghali‐Bostwick C, Varelas X, Tager AM, Tschumperlin DJ. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis. Am J Physiol Lung Cell Mol Physiol 308: L344‐L357, 2015.
 226.Liu F, Mih JD, Shea BS, Kho AT, Sharif AS, Tager AM, Tschumperlin DJ. Feedback amplification of fibrosis through matrix stiffening and COX‐2 suppression. J Cell Biol 190: 693‐706, 2010.
 227.Liu F, Tschumperlin DJ. Micro‐mechanical characterization of lung tissue using atomic force microscopy. J Vis Exp, 2011.
 228.Liu HY, Greene T, Lin TY, Dawes CS, Korc M, Lin CC. Enzyme‐mediated stiffening hydrogels for probing activation of pancreatic stellate cells. Acta Biomater 48: 258‐269, 2017.
 229.Liu HY, Korc M, Lin CC. Biomimetic and enzyme‐responsive dynamic hydrogels for studying cell‐matrix interactions in pancreatic ductal adenocarcinoma. Biomaterials 160: 24‐36, 2018.
 230.Liu L, Zhang SX, Liao W, Farhoodi HP, Wong CW, Chen CC, Ségaliny AI, Chacko JV, Nguyen LP, Lu M, Polovin G, Pone EJ, Downing TL, Lawson DA, Digman MA, Zhao W. Mechanoresponsive stem cells to target cancer metastases through biophysical cues. Sci Transl Med 9: eaan2966, 2017.
 231.Liu S, Young SM, Varisco BM. Dynamic expression of chymotrypsin‐like elastase 1 over the course of murine lung development. Am J Physiol Lung Cell Mol Physiol 306: L1104‐L1116, 2014.
 232.Liu‐Chittenden Y, Huang B, Shim JS, Chen Q, Lee SJ, Anders RA, Liu JO, Pan D. Genetic and pharmacological disruption of the TEAD‐YAP complex suppresses the oncogenic activity of YAP. Genes Dev 26: 1300‐1305, 2012.
 233.Lo CM, Wang HB, Dembo M, Wang YL. Cell movement is guided by the rigidity of the substrate. Biophys J 79: 144‐152, 2000.
 234.Lockhart‐Cairns MP, Newandee H, Thomson J, Weiss AS, Baldock C, Tarakanova A. Transglutaminase‐mediated cross‐linking of tropoelastin to fibrillin stabilises the elastin precursor prior to elastic fibre assembly. J Mol Biol 432: 5736‐5751, 2020.
 235.Long R, Hall MS, Wu M, Hui CY. Effects of gel thickness on microscopic indentation measurements of gel modulus. Biophys J 101: 643‐650, 2011.
 236.Lubinski MA, Emelianov SY, O'Donnell M. Speckle tracking methods for ultrasonic elasticity imaging using short‐time correlation. IEEE Trans Ultrason Ferroelectr Freq Control 46: 82‐96, 1999.
 237.Luft FC. Molecular mechanisms of arterial stiffness: New insights. J Am Soc Hypertens 6: 436‐438, 2012.
 238.Luque T, Melo E, Garreta E, Cortiella J, Nichols J, Farré R, Navajas D. Local micromechanical properties of decellularized lung scaffolds measured with atomic force microscopy. Acta Biomater 9: 6852‐6859, 2013.
 239.Lutolf MP, Lauer‐Fields JL, Schmoekel HG, Metters AT, Weber FE, Fields GB, Hubbell JA. Synthetic matrix metalloproteinase‐sensitive hydrogels for the conduction of tissue regeneration: Engineering cell‐invasion characteristics. Proc Natl Acad Sci U S A 100: 5413‐5418, 2003.
 240.Lyck Hansen M, Beck HC, Irmukhamedov A, Jensen PS, Olsen MH, Rasmussen LM. Proteome analysis of human arterial tissue discloses associations between the vascular content of small leucine‐rich repeat proteoglycans and pulse wave velocity. Arterioscler Thromb Vasc Biol 35: 1896‐1903, 2015.
 241.Macaya D, Spector M. Injectable hydrogel materials for spinal cord regeneration: A review. Biomed Mater 7: 012001, 2012.
 242.Machahua C, Montes‐Worboys A, Llatjos R, Escobar I, Dorca J, Molina‐Molina M, Vicens‐Zygmunt V. Increased AGE‐RAGE ratio in idiopathic pulmonary fibrosis. Respir Res 17: 144, 2016.
 243.Mahapatra S, Nishimura RA, Sorajja P, Cha S, McGoon MD. Relationship of pulmonary arterial capacitance and mortality in idiopathic pulmonary arterial hypertension. J Am Coll Cardiol 47: 799‐803, 2006.
 244.Majedi FS, Hasani‐Sadrabadi MM, Thauland TJ, Li S, Bouchard LS, Butte MJ. T‐cell activation is modulated by the 3D mechanical microenvironment. Biomaterials 252: 120058, 2020.
 245.Mammoto A, Mammoto T, Kanapathipillai M, Wing Yung C, Jiang E, Jiang A, Lofgren K, Gee EP, Ingber DE. Control of lung vascular permeability and endotoxin‐induced pulmonary oedema by changes in extracellular matrix mechanics. Nat Commun 4: 1759, 2013.
 246.Mammoto T, Jiang E, Jiang A, Mammoto A. Extracellular matrix structure and tissue stiffness control postnatal lung development through the lipoprotein receptor‐related protein 5/Tie2 signaling system. Am J Respir Cell Mol Biol 49: 1009‐1018, 2013.
 247.Mann BK, Gobin AS, Tsai AT, Schmedlen RH, West JL. Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: Synthetic ECM analogs for tissue engineering. Biomaterials 22: 3045‐3051, 2001.
 248.Marangon I, Silva AA, Guilbert T, Kolosnjaj‐Tabi J, Marchiol C, Natkhunarajah S, Chamming's F, Ménard‐Moyon C, Bianco A, Gennisson JL, Renault G, Gazeau F. Tumor stiffening, a key determinant of tumor progression, is reversed by nanomaterial‐induced photothermal therapy. Theranostics 7: 329‐343, 2017.
 249.Mariappan YK, Glaser KJ, Ehman RL. Magnetic resonance elastography: A review. Clin Anat 23: 497‐511, 2010.
 250.Marinković A, Liu F, Tschumperlin DJ. Matrices of physiologic stiffness potently inactivate idiopathic pulmonary fibrosis fibroblasts. Am J Respir Cell Mol Biol 48: 422‐430, 2013.
 251.Marinković A, Mih JD, Park JA, Liu F, Tschumperlin DJ. Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF‐β responsiveness. Am J Physiol Lung Cell Mol Physiol 303: L169‐L180, 2012.
 252.Mason BN, Starchenko A, Williams RM, Bonassar LJ, Reinhart‐King CA. Tuning three‐dimensional collagen matrix stiffness independently of collagen concentration modulates endothelial cell behavior. Acta Biomater 9: 4635‐4644, 2013.
 253.Matalon O, Ben‐Shmuel A, Kivelevitz J, Sabag B, Fried S, Joseph N, Noy E, Biber G, Barda‐Saad M. Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP‐1. EMBO J 37, 2018.
 254.Mathai SK, Pedersen BS, Smith K, Russell P, Schwarz MI, Brown KK, Steele MP, Loyd JE, Crapo JD, Silverman EK, Nickerson D, Fingerlin TE, Yang IV, Schwartz DA. Desmoplakin variants are associated with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 193: 1151‐1160, 2016.
 255.Meli VS, Atcha H, Veerasubramanian PK, Nagalla RR, Luu TU, Chen EY, Guerrero‐Juarez CF, Yamaga K, Pandori W, Hsieh JY, Downing TL, Fruman DA, Lodoen MB, Plikus MV, Wang W, Liu WF. YAP‐mediated mechanotransduction tunes the macrophage inflammatory response. Sci Adv 6, 6 (49): eabb8471, 2020.
 256.Melo E, Cárdenes N, Garreta E, Luque T, Rojas M, Navajas D, Farré R. Inhomogeneity of local stiffness in the extracellular matrix scaffold of fibrotic mouse lungs. J Mech Behav Biomed Mater 37: 186‐195, 2014.
 257.Melo E, Garreta E, Luque T, Cortiella J, Nichols J, Navajas D, Farré R. Effects of the decellularization method on the local stiffness of acellular lungs. Tissue Eng Part C Methods 20: 412‐422, 2014.
 258.Meng KP, Majedi FS, Thauland TJ, Butte MJ. Mechanosensing through YAP controls T cell activation and metabolism. J Exp Med 217, 2020.
 259.Meng Z, Qiu Y, Lin KC, Kumar A, Placone JK, Fang C, Wang KC, Lu S, Pan M, Hong AW, Moroishi T, Luo M, Plouffe SW, Diao Y, Ye Z, Park HW, Wang X, Yu FX, Chien S, Wang CY, Ren B, Engler AJ, Guan KL. RAP2 mediates mechanoresponses of the Hippo pathway. Nature 560: 655‐660, 2018.
 260.Mennens SFB, Bolomini‐Vittori M, Weiden J, Joosten B, Cambi A, van den Dries K. Substrate stiffness influences phenotype and function of human antigen‐presenting dendritic cells. Sci Rep 7: 17511, 2017.
 261.Mierke CT, Sauer F, Grosser S, Puder S, Fischer T, Käs JA. The two faces of enhanced stroma: Stroma acts as a tumor promoter and a steric obstacle. NMR Biomed 31: e3831, 2018.
 262.Miralles F, Posern G, Zaromytidou AI, Treisman R. Actin dynamics control SRF activity by regulation of its coactivator MAL. Cell 113: 329‐342, 2003.
 263.Miron‐Mendoza M, Seemann J, Grinnell F. The differential regulation of cell motile activity through matrix stiffness and porosity in three dimensional collagen matrices. Biomaterials 31: 6425‐6435, 2010.
 264.Miyazawa A, Ito S, Asano S, Tanaka I, Sato M, Kondo M, Hasegawa Y. Regulation of PD‐L1 expression by matrix stiffness in lung cancer cells. Biochem Biophys Res Commun 495: 2344‐2349, 2018.
 265.Mižíková I, Pfeffer T, Nardiello C, Surate Solaligue DE, Steenbock H, Tatsukawa H, Silva DM, Vadász I, Herold S, Pease RJ, Iismaa SE, Hitomi K, Seeger W, Brinckmann J, Morty RE. Targeting transglutaminase 2 partially restores extracellular matrix structure but not alveolar architecture in experimental bronchopulmonary dysplasia. FEBS J 285: 3056‐3076, 2018.
 266.Moon JJ, Saik JE, Poché RA, Leslie‐Barbick JE, Lee SH, Smith AA, Dickinson ME, West JL. Biomimetic hydrogels with pro‐angiogenic properties. Biomaterials 31: 3840‐3847, 2010.
 267.Mordechay L, Le Saux G, Edri A, Hadad U, Porgador A, Schvartzman M. Mechanical Regulation of the Cytotoxic Activity of Natural Killer Cells. ACS Biomater Sci Eng 7: 122‐132, 2021.
 268.Muthupillai R, Lomas DJ, Rossman PJ, Greenleaf JF, Manduca A, Ehman RL. Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. Science 269: 1854‐1857, 1995.
 269.Nagy N, de la Zerda A, Kaber G, Johnson PY, Hu KH, Kratochvil MJ, Yadava K, Zhao W, Cui Y, Navarro G, Annes JP, Wight TN, Heilshorn SC, Bollyky PL, Butte MJ. Hyaluronan content governs tissue stiffness in pancreatic islet inflammation. J Biol Chem 293: 567‐578, 2018.
 270.Navab R, Strumpf D, To C, Pasko E, Kim KS, Park CJ, Hai J, Liu J, Jonkman J, Barczyk M, Bandarchi B, Wang YH, Venkat K, Ibrahimov E, Pham NA, Ng C, Radulovich N, Zhu CQ, Pintilie M, Wang D, Lu A, Jurisica I, Walker GC, Gullberg D, Tsao MS. Integrin α11β1 regulates cancer stromal stiffness and promotes tumorigenicity and metastasis in non‐small cell lung cancer. Oncogene 35: 1899‐1908, 2016.
 271.Nave AH, Mižíková I, Niess G, Steenbock H, Reichenberger F, Talavera ML, Veit F, Herold S, Mayer K, Vadász I, Weissmann N, Seeger W, Brinckmann J, Morty RE. Lysyl oxidases play a causal role in vascular remodeling in clinical and experimental pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 34: 1446‐1458, 2014.
 272.Nerem RM, Seliktar D. Vascular tissue engineering. Annu Rev Biomed Eng 3: 225‐243, 2001.
 273.Nichols JE, Niles J, Riddle M, Vargas G, Schilagard T, Ma L, Edward K, La Francesca S, Sakamoto J, Vega S, Ogadegbe M, Mlcak R, Deyo D, Woodson L, McQuitty C, Lick S, Beckles D, Melo E, Cortiella J. Production and assessment of decellularized pig and human lung scaffolds. Tissue Eng Part A 19: 2045‐2062, 2013.
 274.Nightingale K, Soo MS, Nightingale R, Trahey G. Acoustic radiation force impulse imaging: In vivo demonstration of clinical feasibility. Ultrasound Med Biol 28: 227‐235, 2002.
 275.Nonaka PN, Uriarte JJ, Campillo N, Melo E, Navajas D, Farré R, Oliveira LV. Mechanical properties of mouse lungs along organ decellularization by sodium dodecyl sulfate. Respir Physiol Neurobiol 200: 1‐5, 2014.
 276.Nowak AP, Breedveld V, Pakstis L, Ozbas B, Pine DJ, Pochan D, Deming TJ. Rapidly recovering hydrogel scaffolds from self‐assembling diblock copolypeptide amphiphiles. Nature 417: 424‐428, 2002.
 277.Oakes PW, Patel DC, Morin NA, Zitterbart DP, Fabry B, Reichner JS, Tang JX. Neutrophil morphology and migration are affected by substrate elasticity. Blood 114: 1387‐1395, 2009.
 278.O'Brien XM, Loosley AJ, Oakley KE, Tang JX, Reichner JS. Technical advance: Introducing a novel metric, directionality time, to quantify human neutrophil chemotaxis as a function of matrix composition and stiffness. J Leukoc Biol 95: 993‐1004, 2014.
 279.O'Connor RS, Hao X, Shen K, Bashour K, Akimova T, Hancock WW, Kam LC, Milone MC. Substrate rigidity regulates human T cell activation and proliferation. J Immunol 189: 1330‐1339, 2012.
 280.Oh K, Park HB, Byoun OJ, Shin DM, Jeong EM, Kim YW, Kim YS, Melino G, Kim IG, Lee DS. Epithelial transglutaminase 2 is needed for T cell interleukin‐17 production and subsequent pulmonary inflammation and fibrosis in bleomycin‐treated mice. J Exp Med 208: 1707‐1719, 2011.
 281.Oh RS, Haak AJ, Smith KMJ, Ligresti G, Choi KM, Xie T, Wang S, Walters PR, Thompson MA, Freeman MR, Manlove LJ, Chu VM, Feghali‐Bostwick C, Roden AC, Schymeinsky J, Pabelick CM, Prakash YS, Vassallo R, Tschumperlin DJ. RNAi screening identifies a mechanosensitive ROCK‐JAK2‐STAT3 network central to myofibroblast activation. J Cell Sci 131, 2018.
 282.Oh SH, An DB, Kim TH, Lee JH. Wide‐range stiffness gradient PVA/HA hydrogel to investigate stem cell differentiation behavior. Acta Biomater 35: 23‐31, 2016.
 283.Ohashi K, Fujiwara S, Mizuno K. Roles of the cytoskeleton, cell adhesion and rho signalling in mechanosensing and mechanotransduction. J Biochem 161: 245‐254, 2017.
 284.Ohlmeier S, Nieminen P, Gao J, Kanerva T, Rönty M, Toljamo T, Bergmann U, Mazur W, Pulkkinen V. Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol 310: L1155‐L1165, 2016.
 285.Okamoto T, Takagi Y, Kawamoto E, Park EJ, Usuda H, Wada K, Shimaoka M. Reduced substrate stiffness promotes M2‐like macrophage activation and enhances peroxisome proliferator‐activated receptor gamma expression. Exp Cell Res 367: 264‐273, 2018.
 286.O'Leary LE, Fallas JA, Bakota EL, Kang MK, Hartgerink JD. Multi‐hierarchical self‐assembly of a collagen mimetic peptide from triple helix to nanofibre and hydrogel. Nat Chem 3: 821‐828, 2011.
 287.Olsen KC, Sapinoro RE, Kottmann RM, Kulkarni AA, Iismaa SE, Johnson GV, Thatcher TH, Phipps RP, Sime PJ. Transglutaminase 2 and its role in pulmonary fibrosis. Am J Respir Crit Care Med 184: 699‐707, 2011.
 288.Onochie OE, Zollinger A, Rich CB, Smith M, Trinkaus‐Randall V. Epithelial cells exert differential traction stress in response to substrate stiffness. Exp Eye Res 181: 25‐37, 2019.
 289.Ophir J, Céspedes I, Ponnekanti H, Yazdi Y, Li X. Elastography: A quantitative method for imaging the elasticity of biological tissues. Ultrason Imaging 13: 111‐134, 1991.
 290.Osman M, Cantor JO, Roffman S, Keller S, Turino GM, Mandl I. Cigarette smoke impairs elastin resynthesis in lungs of hamsters with elastase‐induced emphysema. Am Rev Respir Dis 132: 640‐643, 1985.
 291.Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, Ikonomou L, Kotton D, Vacanti JP. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med 16: 927‐933, 2010.
 292.Pampaloni F, Reynaud EG, Stelzer EH. The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol 8: 839‐845, 2007.
 293.Pankova D, Jiang Y, Chatzifrangkeskou M, Vendrell I, Buzzelli J, Ryan A, Brown C, O'Neill E. RASSF1A controls tissue stiffness and cancer stem‐like cells in lung adenocarcinoma. EMBO J 38: e100532, 2019.
 294.Pankova D, Jiang Y, Chatzifrangkeskou M, Vendrell I, Buzzelli J, Ryan A, Brown C, O'Neill E. RASSF 1A controls tissue stiffness and cancer stem‐like cells in lung adenocarcinoma. The EMBO J 38: e100532, 2019.
 295.Parameswaran K, Willems‐Widyastuti A, Alagappan VK, Radford K, Kranenburg AR, Sharma HS. Role of extracellular matrix and its regulators in human airway smooth muscle biology. Cell Biochem Biophys 44: 139‐146, 2006.
 296.Park JS, Burckhardt CJ, Lazcano R, Solis LM, Isogai T, Li L, Chen CS, Gao B, Minna JD, Bachoo R, DeBerardinis RJ, Danuser G. Mechanical regulation of glycolysis via cytoskeleton architecture. Nature 578: 621‐626, 2020.
 297.Park JS, Chu JS, Tsou AD, Diop R, Tang Z, Wang A, Li S. The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF‐β. Biomaterials 32: 3921‐3930, 2011.
 298.Patel NR, Bole M, Chen C, Hardin CC, Kho AT, Mih J, Deng L, Butler J, Tschumperlin D, Fredberg JJ, Krishnan R, Koziel H. Cell elasticity determines macrophage function. PLoS One 7: e41024, 2012.
 299.Pedersen JA, Swartz MA. Mechanobiology in the third dimension. Ann Biomed Eng 33: 1469‐1490, 2005.
 300.Pelham RJ Jr, Wang Y. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci U S A 94: 13661‐13665, 1997.
 301.Pelham RJ, Wang YL. Cell locomotion and focal adhesions are regulated by the mechanical properties of the substrate. Biol Bull 194: 348‐349; discussion 349‐350, 1998.
 302.Pereira RF, Barrias CC, Bártolo PJ, Granja PL. Cell‐instructive pectin hydrogels crosslinked via thiol‐norbornene photo‐click chemistry for skin tissue engineering. Acta Biomater 66: 282‐293, 2018.
 303.Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, Gavrilov K, Yi T, Zhuang ZW, Breuer C, Herzog E, Niklason LE. Tissue‐engineered lungs for in vivo implantation. Science 329: 538‐541, 2010.
 304.Peyton SR, Putnam AJ. Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion. J Cell Physiol 204: 198‐209, 2005.
 305.Phelps EA, Enemchukwu NO, Fiore VF, Sy JC, Murthy N, Sulchek TA, Barker TH, García AJ. Maleimide cross‐linked bioactive PEG hydrogel exhibits improved reaction kinetics and cross‐linking for cell encapsulation and in situ delivery. Adv Mater 24: 64‐70, 62, 2012.
 306.Philp CJ, Siebeke I, Clements D, Miller S, Habgood A, John AE, Navaratnam V, Hubbard RB, Jenkins G, Johnson SR. Extracellular matrix cross‐linking enhances fibroblast growth and protects against matrix proteolysis in lung fibrosis. Am J Respir Cell Mol Biol 58: 594‐603, 2018.
 307.Pogoda K, Bucki R, Byfield FJ, Cruz K, Lee T, Marcinkiewicz C, Janmey PA. Soft substrates containing hyaluronan mimic the effects of increased stiffness on morphology, motility, and proliferation of glioma cells. Biomacromolecules 18: 3040‐3051, 2017.
 308.Polio SR, Stasiak SE, Jamieson RR, Balestrini JL, Krishnan R, Parameswaran H. Extracellular matrix stiffness regulates human airway smooth muscle contraction by altering the cell‐cell coupling. Sci Rep 9: 9564, 2019.
 309.Prantil‐Baun R, Novak R, Das D, Somayaji MR, Przekwas A, Ingber DE. Physiologically based pharmacokinetic and pharmacodynamic analysis enabled by microfluidically linked organs‐on‐chips. Annu Rev Pharmacol Toxicol 58: 37‐64, 2018.
 310.Price AP, England KA, Matson AM, Blazar BR, Panoskaltsis‐Mortari A. Development of a decellularized lung bioreactor system for bioengineering the lung: The matrix reloaded. Tissue Eng Part A 16: 2581‐2591, 2010.
 311.Puig M, Lugo R, Gabasa M, Giménez A, Velásquez A, Galgoczy R, Ramírez J, Gómez‐Caro A, Busnadiego Ó, Rodríguez‐Pascual F. Matrix stiffening and β1 integrin drive subtype‐specific fibroblast accumulation in lung cancer. Molecul Cancer Res 13: 161‐173, 2015.
 312.Qu J, Yang SZ, Zhu Y, Guo T, Thannickal VJ, Zhou Y. Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice. J Exp Med 218, 2021.
 313.Qu J, Zhu L, Zhou Z, Chen P, Liu S, Locy ML, Thannickal VJ, Zhou Y. Reversing mechanoinductive DSP expression by CRISPR/dCas9‐mediated epigenome editing. Am J Respir Crit Care Med 198: 599‐609, 2018.
 314.Raghu G, Brown KK, Collard HR, Cottin V, Gibson KF, Kaner RJ, Lederer DJ, Martinez FJ, Noble PW, Song JW, Wells AU, Whelan TP, Wuyts W, Moreau E, Patterson SD, Smith V, Bayly S, Chien JW, Gong Q, Zhang JJ, O'Riordan TG. Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: A randomised, double‐blind, controlled, phase 2 trial. Lancet Respir Med 5: 22‐32, 2017.
 315.Rahaman SO, Grove LM, Paruchuri S, Southern BD, Abraham S, Niese KA, Scheraga RG, Ghosh S, Thodeti CK, Zhang DX, Moran MM, Schilling WP, Tschumperlin DJ, Olman MA. TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice. J Clin Invest 124: 5225‐5238, 2014.
 316.Raqeeb A, Jiao Y, Syyong HT, Paré PD, Seow CY. Regulatable stiffness in relaxed airway smooth muscle: A target for asthma treatment? J Appl Physiol 112 (337‐346): 2012, 1985.
 317.Reagan MR, Kaplan DL. Concise review: Mesenchymal stem cell tumor‐homing: Detection methods in disease model systems. Stem Cells 29: 920‐927, 2011.
 318.Rehfeldt F, Engler AJ, Eckhardt A, Ahmed F, Discher DE. Cell responses to the mechanochemical microenvironment‐‐implications for regenerative medicine and drug delivery. Adv Drug Deliv Rev 59: 1329‐1339, 2007.
 319.Riento K, Ridley AJ. Rocks: Multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 4: 446‐456, 2003.
 320.Robinson KA, Sun M, Barnum CE, Weiss SN, Huegel J, Shetye SS, Lin L, Saez D, Adams SM, Iozzo RV, Soslowsky LJ, Birk DE. Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons. Matrix Biol 64: 81‐93, 2017.
 321.Roeder BA, Kokini K, Sturgis JE, Robinson JP, Voytik‐Harbin SL. Tensile mechanical properties of three‐dimensional type I collagen extracellular matrices with varied microstructure. J Biomech Eng 124: 214‐222, 2002.
 322.Rogers CI, Qaderi K, Woolley AT, Nordin GP. 3D printed microfluidic devices with integrated valves. Biomicrofluidics 9, 2015. DOI: 016501.
 323.Rosales AM, Anseth KS. The design of reversible hydrogels to capture extracellular matrix dynamics. Nat Rev Mater 1, 2016. DOI: 15012.
 324.Rosales AM, Vega SL, DelRio FW, Burdick JA, Anseth KS. Hydrogels with reversible mechanics to probe dynamic cell microenvironments. Angew Chem Int Ed Engl 56: 12132‐12136, 2017.
 325.Rozario T, Dzamba B, Weber GF, Davidson LA, DeSimone DW. The physical state of fibronectin matrix differentially regulates morphogenetic movements in vivo. Dev Biol 327: 386‐398, 2009.
 326.Ruffenach G, Chabot S, Tanguay VF, Courboulin A, Boucherat O, Potus F, Meloche J, Pflieger A, Breuils‐Bonnet S, Nadeau V, Paradis R, Tremblay E, Girerd B, Hautefort A, Montani D, Fadel E, Dorfmuller P, Humbert M, Perros F, Paulin R, Provencher S, Bonnet S. Role for runt‐related transcription factor 2 in proliferative and calcified vascular lesions in pulmonary arterial hypertension. Am J Respir Crit Care Med 194: 1273‐1285, 2016.
 327.Sakai T, Larsen M, Yamada KM. Fibronectin requirement in branching morphogenesis. Nature 423: 876‐881, 2003.
 328.Salameh N, Larrat B, Abarca‐Quinones J, Pallu S, Dorvillius M, Leclercq I, Fink M, Sinkus R, Van Beers BE. Early detection of steatohepatitis in fatty rat liver by using MR elastography. Radiology 253: 90‐97, 2009.
 329.Samuel MS, Lopez JI, McGhee EJ, Croft DR, Strachan D, Timpson P, Munro J, Schröder E, Zhou J, Brunton VG, Barker N, Clevers H, Sansom OJ, Anderson KI, Weaver VM, Olson MF. Actomyosin‐mediated cellular tension drives increased tissue stiffness and β‐catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell 19: 776‐791, 2011.
 330.Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R. Transient elastography: A new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 29: 1705‐1713, 2003.
 331.Sarvazyan AP, Rudenko OV, Swanson SD, Fowlkes JB, Emelianov SY. Shear wave elasticity imaging: A new ultrasonic technology of medical diagnostics. Ultrasound Med Biol 24: 1419‐1435, 1998.
 332.Sato S, Chong SG, Upagupta C, Yanagihara T, Saito T, Shimbori C, Bellaye PS, Nishioka Y, Kolb MR. Fibrotic extracellular matrix induces release of extracellular vesicles with pro‐fibrotic miRNA from fibrocytes. Thorax, 2021.
 333.Saums MK, Wang W, Han B, Madhavan L, Han L, Lee D, Wells RG. Mechanically and chemically tunable cell culture system for studying the myofibroblast phenotype. Langmuir 30: 5481‐5487, 2014.
 334.Saxena N, Mogha P, Dash S, Majumder A, Jadhav S, Sen S. Matrix elasticity regulates mesenchymal stem cell chemotaxis. J Cell Sci 131, 2018.
 335.Schäfer M, Myers C, Brown RD, Frid MG, Tan W, Hunter K, Stenmark KR. Pulmonary arterial stiffness: Toward a new paradigm in pulmonary arterial hypertension pathophysiology and assessment. Curr Hypertens Rep 18: 4, 2016.
 336.Schiller HB, Hermann MR, Polleux J, Vignaud T, Zanivan S, Friedel CC, Sun Z, Raducanu A, Gottschalk KE, Théry M, Mann M, Fässler R. β1‐ and αv‐class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin‐based microenvironments. Nat Cell Biol 15: 625‐636, 2013.
 337.Schittny JC, Paulsson M, Vallan C, Burri PH, Kedei N, Aeschlimann D. Protein cross‐linking mediated by tissue transglutaminase correlates with the maturation of extracellular matrices during lung development. Am J Respir Cell Mol Biol 17: 334‐343, 1997.
 338.Scholze A, Bladbjerg EM, Sidelmann JJ, Diederichsen AC, Mickley H, Nybo M, Argraves WS, Marckmann P, Rasmussen LM. Plasma concentrations of extracellular matrix protein fibulin‐1 are related to cardiovascular risk markers in chronic kidney disease and diabetes. Cardiovasc Diabetol 12: 6, 2013.
 339.Schuliga M, Grainge C, Westall G, Knight D. The fibrogenic actions of the coagulant and plasminogen activation systems in pulmonary fibrosis. Int J Biochem Cell Biol 97: 108‐117, 2018.
 340.Scott JE. Proteoglycan: Collagen interactions and corneal ultrastructure. Biochem Soc Trans 19: 877‐881, 1991.
 341.Scott JE. Supramolecular organization of extracellular matrix glycosaminoglycans, in vitro and in the tissues. FASEB J 6: 2639‐2645, 1992.
 342.Seidlits SK, Khaing ZZ, Petersen RR, Nickels JD, Vanscoy JE, Shear JB, Schmidt CE. The effects of hyaluronic acid hydrogels with tunable mechanical properties on neural progenitor cell differentiation. Biomaterials 31: 3930‐3940, 2010.
 343.Selman M, Montaño M, Ramos C, Vanda B, Becerril C, Delgado J, Sansores R, Barrios R, Pardo A. Tobacco smoke‐induced lung emphysema in guinea pigs is associated with increased interstitial collagenase. Am J Physiol 271: L734‐L743, 1996.
 344.Seow CY. Passive stiffness of airway smooth muscle: The next target for improving airway distensibility and treatment for asthma? Pulm Pharmacol Ther 26: 37‐41, 2013.
 345.Shah MA, Scaman CH, Palcic MM, Kagan HM. Kinetics and stereospecificity of the lysyl oxidase reaction. J Biol Chem 268: 11573‐11579, 1993.
 346.Shaheen S, Wan Z, Li Z, Chau A, Li X, Zhang S, Liu Y, Yi J, Zeng Y, Wang J, Chen X, Xu L, Chen W, Wang F, Lu Y, Zheng W, Shi Y, Sun X, Li Z, Xiong C, Liu W. Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCbeta and focal adhesion kinase. Elife 6: e23063, 2017.
 347.Shkumatov A, Thompson M, Choi KM, Sicard D, Baek K, Kim DH, Tschumperlin DJ, Prakash YS, Kong H. Matrix stiffness‐modulated proliferation and secretory function of the airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 308: L1125‐L1135, 2015.
 348.Sicard D, Haak AJ, Choi KM, Craig AR, Fredenburgh LE, Tschumperlin DJ. Aging and anatomical variations in lung tissue stiffness. Am J Physiol Lung Cell Mol Physiol 314: L946‐L955, 2018.
 349.Sieminski AL, Hebbel RP, Gooch KJ. The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro. Exp Cell Res 297: 574‐584, 2004.
 350.Sinkus R, Siegmann K, Xydeas T, Tanter M, Claussen C, Fink M. MR elastography of breast lesions: Understanding the solid/liquid duality can improve the specificity of contrast‐enhanced MR mammography. Magn Reson Med 58: 1135‐1144, 2007.
 351.Sinkus R, Tanter M, Xydeas T, Catheline S, Bercoff J, Fink M. Viscoelastic shear properties of in vivo breast lesions measured by MR elastography. Magn Reson Imaging 23: 159‐165, 2005.
 352.Sisson TH, Ajayi IO, Subbotina N, Dodi AE, Rodansky ES, Chibucos LN, Kim KK, Keshamouni VG, White ES, Zhou Y, Higgins PD, Larsen SD, Neubig RR, Horowitz JC. Inhibition of myocardin‐related transcription factor/serum response factor signaling decreases lung fibrosis and promotes mesenchymal cell apoptosis. Am J Pathol 185: 969‐986, 2015.
 353.Sisson TH, Simon RH. The plasminogen activation system in lung disease. Curr Drug Targets 8: 1016‐1029, 2007.
 354.Sokocevic D, Bonenfant NR, Wagner DE, Borg ZD, Lathrop MJ, Lam YW, Deng B, Desarno MJ, Ashikaga T, Loi R, Hoffman AM, Weiss DJ. The effect of age and emphysematous and fibrotic injury on the re‐cellularization of de‐cellularized lungs. Biomaterials 34: 3256‐3269, 2013.
 355.Soucy PA, Werbin J, Heinz W, Hoh JH, Romer LH. Microelastic properties of lung cell‐derived extracellular matrix. Acta Biomater 7: 96‐105.
 356.Southern BD, Grove LM, Rahaman SO, Abraham S, Scheraga RG, Niese KA, Sun H, Herzog EL, Liu F, Tschumperlin DJ, Egelhoff TT, Rosenfeld SS, Olman MA. Matrix‐driven myosin II mediates the pro‐fibrotic fibroblast phenotype. J Biol Chem 291: 6083‐6095, 2016.
 357.Speight P, Kofler M, Szászi K, Kapus A. Context‐dependent switch in chemo/mechanotransduction via multilevel crosstalk among cytoskeleton‐regulated MRTF and TAZ and TGFβ‐regulated Smad3. Nat Commun 7: 11642, 2016.
 358.Sridharan R, Cavanagh B, Cameron AR, Kelly DJ, O'Brien FJ. Material stiffness influences the polarization state, function and migration mode of macrophages. Acta Biomater 89: 47‐59, 2019.
 359.STEINBERG MS. Reconstruction of tissues by dissociated cells. Some morphogenetic tissue movements and the sorting out of embryonic cells may have a common explanation. Science 141: 401‐408, 1963.
 360.Stephens P, Grenard P, Aeschlimann P, Langley M, Blain E, Errington R, Kipling D, Thomas D, Aeschlimann D. Crosslinking and G‐protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses. J Cell Sci 117: 3389‐3403, 2004.
 361.Stone PJ, Gottlieb DJ, O'Connor GT, Ciccolella DE, Breuer R, Bryan‐Rhadfi J, Shaw HA, Franzblau C, Snider GL. Elastin and collagen degradation products in urine of smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med 151: 952‐959, 1995.
 362.Stowers RS, Allen SC, Suggs LJ. Dynamic phototuning of 3D hydrogel stiffness. Proc Natl Acad Sci U S A 112: 1953‐1958, 2015.
 363.Stowers RS, Shcherbina A, Israeli J, Gruber JJ, Chang J, Nam S, Rabiee A, Teruel MN, Snyder MP, Kundaje A, Chaudhuri O. Matrix stiffness induces a tumorigenic phenotype in mammary epithelium through changes in chromatin accessibility. Nat Biomed Eng 3: 1009‐1019, 2019.
 364.Streitberger KJ, Sack I, Krefting D, Pfüller C, Braun J, Paul F, Wuerfel J. Brain viscoelasticity alteration in chronic‐progressive multiple sclerosis. PLoS One 7: e29888, 2012.
 365.Stroka KM, Aranda‐Espinoza H. Neutrophils display biphasic relationship between migration and substrate stiffness. Cell Motil Cytoskeleton 66: 328‐341, 2009.
 366.Stroka KM, Aranda‐Espinoza H. Endothelial cell substrate stiffness influences neutrophil transmigration via myosin light chain kinase‐dependent cell contraction. Blood 118: 1632‐1640, 2011.
 367.Stroka KM, Levitan I, Aranda‐Espinoza H. OxLDL and substrate stiffness promote neutrophil transmigration by enhanced endothelial cell contractility and ICAM‐1. J Biomech 45: 1828‐1834, 2012.
 368.Suh JK, Matthew HW. Application of chitosan‐based polysaccharide biomaterials in cartilage tissue engineering: A review. Biomaterials 21: 2589‐2598, 2000.
 369.Suki B. Assessing the functional mechanical properties of bioengineered organs with emphasis on the lung. J Cell Physiol 229: 1134‐1140, 2014.
 370.Sun W, Chan SY. Pulmonary arterial stiffness: An early and pervasive driver of pulmonary arterial hypertension. Front Med (Lausanne) 5: 204, 2018.
 371.Sun Z, Guo SS, Fässler R. Integrin‐mediated mechanotransduction. J Cell Biol 215: 445‐456, 2016.
 372.Sunyer R, Jin AJ, Nossal R, Sackett DL. Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response. PLoS One 7: e46107, 2012.
 373.Sweers KK, Bennink ML, Subramaniam V. Nanomechanical properties of single amyloid fibrils. J Phys Condens Matter 24: 243101, 2012.
 374.Swift J, Ivanovska IL, Buxboim A, Harada T, Dingal PC, Pinter J, Pajerowski JD, Spinler KR, Shin JW, Tewari M, Rehfeldt F, Speicher DW, Discher DE. Nuclear lamin‐A scales with tissue stiffness and enhances matrix‐directed differentiation. Science 341: 1240104, 2013.
 375.Szeto SG, Narimatsu M, Lu M, He X, Sidiqi AM, Tolosa MF, Chan L, De Freitas K, Bialik JF, Majumder S, Boo S, Hinz B, Dan Q, Advani A, John R, Wrana JL, Kapus A, Yuen DA. YAP/TAZ are mechanoregulators of TGF. J Am Soc Nephrol 27: 3117‐3128, 2016.
 376.Tan JL, Tien J, Pirone DM, Gray DS, Bhadriraju K, Chen CS. Cells lying on a bed of microneedles: An approach to isolate mechanical force. Proc Natl Acad Sci U S A 100: 1484‐1489, 2003.
 377.Tapial Martínez P, López Navajas P, Lietha D. FAK structure and regulation by membrane interactions and force in focal adhesions. Biomolecules 10, 2020.
 378.Tatler AL, John AE, Jolly L, Habgood A, Porte J, Brightling C, Knox AJ, Pang L, Sheppard D, Huang X, Jenkins G. Integrin αvβ5‐mediated TGF‐β activation by airway smooth muscle cells in asthma. J Immunol 187: 6094‐6107, 2011.
 379.Tazdait M, Mezquita L, Lahmar J, Ferrara R, Bidault F, Ammari S, Balleyguier C, Planchard D, Gazzah A, Soria J. Patterns of responses in metastatic NSCLC during PD‐1 or PDL‐1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria. Eu J Cancer 88: 38‐47, 2018.
 380.Thiele J, Ma Y, Bruekers SM, Ma S, Huck WT. 25th anniversary article: Designer hydrogels for cell cultures: A materials selection guide. Adv Mater 26: 125‐147, 2014.
 381.Tian B, Manley JL. Alternative polyadenylation of mRNA precursors. Nat Rev Mol Cell Biol 18: 18‐30, 2017.
 382.Tian W, Hao C, Fan Z, Weng X, Qin H, Wu X, Fang M, Chen Q, Shen A, Xu Y. Myocardin related transcription factor A programs epigenetic activation of hepatic stellate cells. J Hepatol 62: 165‐174, 2015.
 383.Tibbitt MW, Anseth KS. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng 103: 655‐663, 2009.
 384.Tjin G, White ES, Faiz A, Sicard D, Tschumperlin DJ, Mahar A, Kable EPW, Burgess JK. Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis. Dis Model Mech 10: 1301‐1312, 2017.
 385.Todorovic V, Jurukovski V, Chen Y, Fontana L, Dabovic B, Rifkin DB. Latent TGF‐beta binding proteins. Int J Biochem Cell Biol 37: 38‐41, 2005.
 386.Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano‐regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3: 349‐363, 2002.
 387.Torrino S, Roustan FR, Kaminski L, Bertero T, Pisano S, Ambrosetti D, Dufies M, Uhler JP, Lemichez E, Mettouchi A. UBTD1 is a mechano‐regulator controlling cancer aggressiveness. EMBO Rep 20: e46570, 2019.
 388.Totaro A, Castellan M, Battilana G, Zanconato F, Azzolin L, Giulitti S, Cordenonsi M, Piccolo S. YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate. Nat Commun 8: 15206, 2017.
 389.Trappmann B, Chen CS. How cells sense extracellular matrix stiffness: A material's perspective. Curr Opin Biotechnol 24: 948‐953, 2013.
 390.Trappmann B, Gautrot JE, Connelly JT, Strange DG, Li Y, Oyen ML, Cohen Stuart MA, Boehm H, Li B, Vogel V, Spatz JP, Watt FM, Huck WT. Extracellular‐matrix tethering regulates stem‐cell fate. Nat Mater 11: 642‐649, 2012.
 391.Truby RL, Lewis JA. Printing soft matter in three dimensions. Nature 540: 371‐378, 2016.
 392.Tschumperlin DJ. Matrix, mesenchyme, and mechanotransduction. Ann Am Thorac Soc 12 (Suppl 1): S24‐S29, 2015.
 393.Tschumperlin DJ, Lagares D. Mechano‐therapeutics: Targeting mechanical signaling in fibrosis and tumor stroma. Pharmacol Ther 107575, 2020.
 394.Tse JR, Engler AJ. Preparation of hydrogel substrates with tunable mechanical properties. Curr Protoc Cell Biol. Chapter 10: Unit 10: 16, 2010.
 395.Tse JR, Engler AJ. Stiffness gradients mimicking in vivo tissue variation regulate mesenchymal stem cell fate. PLoS One 6: e15978, 2011.
 396.Tsochatzis EA, Gurusamy KS, Ntaoula S, Cholongitas E, Davidson BR, Burroughs AK. Elastography for the diagnosis of severity of fibrosis in chronic liver disease: A meta‐analysis of diagnostic accuracy. J Hepatol 54: 650‐659, 2011.
 397.Ulrich P, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res 56: 1‐21, 2001.
 398.Urciuoli E, Peruzzi B. Involvement of the FAK Network in pathologies related to altered mechanotransduction. Int J Mol Sci 21, 2020.
 399.Venkatasubramanian RT, Wolkers WF, Shenoi MM, Barocas VH, Lafontaine D, Soule CL, Iaizzo PA, Bischof JC. Freeze‐thaw induced biomechanical changes in arteries: Role of collagen matrix and smooth muscle cells. Ann Biomed Eng 38: 694‐706, 2010.
 400.Vining KH, Mooney DJ. Mechanical forces direct stem cell behaviour in development and regeneration. Nat Rev Mol Cell Biol 18: 728‐742, 2017.
 401.Wagenseil JE, Mecham RP. Elastin in large artery stiffness and hypertension. J Cardiovasc Transl Res 5: 264‐273, 2012.
 402.Wagh AA, Roan E, Chapman KE, Desai LP, Rendon DA, Eckstein EC, Waters CM. Localized elasticity measured in epithelial cells migrating at a wound edge using atomic force microscopy. Am J Physiol Lung Cell Mol Physiol 295: L54‐L60, 2008.
 403.Walker CJ, Crocini C, Ramirez D, Killaars AR, Grim JC, Aguado BA, Clark K, Allen MA, Dowell RD, Leinwand LA, Anseth KS. Nuclear mechanosensing drives chromatin remodelling in persistently activated fibroblasts. Nat. Biomed Eng, 2021.
 404.Wallis JM, Borg ZD, Daly AB, Deng B, Ballif BA, Allen GB, Jaworski DM, Weiss DJ. Comparative assessment of detergent‐based protocols for mouse lung de‐cellularization and re‐cellularization. Tissue Eng Part C Methods 18: 420‐432, 2012.
 405.Walraven M, Hinz B. Therapeutic approaches to control tissue repair and fibrosis: Extracellular matrix as a game changer. Matrix Biol 71–72: 205‐224, 2018.
 406.Wang JY, Mesquida P, Lee T. Young's modulus measurement on pig trachea and bronchial airways. Annu Int Conf IEEE Eng Med Biol Soc 2089‐2092: 2011, 2011.
 407.Wang T, Hamilla S, Cam M, Aranda‐Espinoza H, Mili S. Extracellular matrix stiffness and cell contractility control RNA localization to promote cell migration. Nat Commun 8: 896, 2017.
 408.Wang W, Lollis EM, Bordeleau F, Reinhart‐King CA. Matrix stiffness regulates vascular integrity through focal adhesion kinase activity. FASEB J 33: 1199‐1208, 2019.
 409.Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, Damsky C, Bissell MJ. Reversion of the malignant phenotype of human breast cells in three‐dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol 137: 231‐245, 1997.
 410.Webber MJ, Tongers J, Newcomb CJ, Marquardt KT, Bauersachs J, Losordo DW, Stupp SI. Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair. Proc Natl Acad Sci U S A 108: 13438‐13443, 2011.
 411.Wei Y, Dong W, Jackson J, Ho TC, Le Saux CJ, Brumwell A, Li X, Klesney‐Tait J, Cohen ML, Wolters PJ, Chapman HA. Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision‐cut lung slices derived from patients with idiopathic pulmonary fibrosis. Thorax, 2021.
 412.Wen JH, Vincent LG, Fuhrmann A, Choi YS, Hribar KC, Taylor‐Weiner H, Chen S, Engler AJ. Interplay of matrix stiffness and protein tethering in stem cell differentiation. Nat Mater 13: 979‐987, 2014.
 413.Weng T, Ko J, Masamha CP, Xia Z, Xiang Y, Chen NY, Molina JG, Collum S, Mertens TC, Luo F, Philip K, Davies J, Huang J, Wilson C, Thandavarayan RA, Bruckner BA, Jyothula SS, Volcik KA, Li L, Han L, Li W, Assassi S, Karmouty‐Quintana H, Wagner EJ, Blackburn MR. Cleavage factor 25 deregulation contributes to pulmonary fibrosis through alternative polyadenylation. J Clin Invest 130, 2019.
 414.Wetzl V, Tiede SL, Faerber L, Weissmann N, Schermuly RT, Ghofrani HA, Gall H. Plasma MMP2/TIMP4 ratio at follow‐up assessment predicts disease progression of idiopathic pulmonary arterial hypertension. Lung 195: 489‐496, 2017.
 415.Wilgus ML, Borczuk AC, Stoopler M, Ginsburg M, Gorenstein L, Sonett JR, Powell CA. Lysyl oxidase: A lung adenocarcinoma biomarker of invasion and survival. Cancer 117: 2186‐2191, 2011.
 416.Wilson JW, Li X, Pain MC. The lack of distensibility of asthmatic airways. Am Rev Respir Dis 148: 806‐809, 1993.
 417.Wilusz RE, Defrate LE, Guilak F. A biomechanical role for perlecan in the pericellular matrix of articular cartilage. Matrix Biol 31: 320‐327, 2012.
 418.Wipff PJ, Rifkin DB, Meister JJ, Hinz B. Myofibroblast contraction activates latent TGF‐beta1 from the extracellular matrix. J Cell Biol 179: 1311‐1323, 2007.
 419.Witsch TJ, Niess G, Sakkas E, Likhoshvay T, Becker S, Herold S, Mayer K, Vadász I, Roberts JD, Seeger W, Morty RE. Transglutaminase 2: A new player in bronchopulmonary dysplasia? Eur Respir J 44: 109‐121, 2014.
 420.Wood JA, Shah NM, McKee CT, Hughbanks ML, Liliensiek SJ, Russell P, Murphy CJ. The role of substratum compliance of hydrogels on vascular endothelial cell behavior. Biomaterials 32: 5056‐5064, 2011.
 421.Woodcock CC, Hafeez N, Handen A, Tang Y, Harvey LD, Estephan LE, Speyer G, Kim S, Bertero T, Chan SY. Matrix stiffening induces a pathogenic QKI‐miR‐7‐SRSF1 signaling axis in pulmonary arterial endothelial cells. Am J Physiol Lung Cell Mol Physiol, 2021.
 422.Wouters OY, Ploeger DT, van Putten SM, Bank RA. 3,4‐Dihydroxy‐L‐phenylalanine as a novel covalent linker of extracellular matrix proteins to polyacrylamide hydrogels with a tunable stiffness. Tissue Eng Part C Methods, 2016.
 423.Xia T, Liu W, Yang L. A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine. J Biomed Mater Res A 105: 1799‐1812, 2017.
 424.Xia XD, Lee J, Khan S, Ye L, Li Y, Dong L. Suppression of phosphatidylinositol 3‐kinase/Akt signaling attenuates hypoxia‐induced pulmonary hypertension through the downregulation of Lysyl oxidase. DNA Cell Biol 35: 599‐606, 2016.
 425.Xie SA, Zhang T, Wang J, Zhao F, Zhang YP, Yao WJ, Hur SS, Yeh YT, Pang W, Zheng LS, Fan YB, Kong W, Wang X, Chiu JJ, Zhou J. Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro and in vivo: Role of DNA methyltransferase 1. Biomaterials 155: 203‐216, 2018.
 426.Xu MY, Porte J, Knox AJ, Weinreb PH, Maher TM, Violette SM, McAnulty RJ, Sheppard D, Jenkins G. Lysophosphatidic acid induces alphavbeta6 integrin‐mediated TGF‐beta activation via the LPA2 receptor and the small G protein G alpha(q). Am J Pathol 174: 1264‐1279, 2009.
 427.Xu X, Li Z, Cai L, Calve S, Neu CP. Mapping the nonreciprocal micromechanics of individual cells and the surrounding matrix within living tissues. Sci Rep 6: 24272, 2016.
 428.Xu X, Li Z, Leng Y, Neu CP, Calve S. Knockdown of the pericellular matrix molecule perlecan lowers in situ cell and matrix stiffness in developing cartilage. Dev Biol 418: 242‐247, 2016.
 429.Yamashita H, Ichikawa T, Matsuyama D, Kimura Y, Ueda K, Craig SW, Harada I, Kioka N. The role of the interaction of the vinculin proline‐rich linker region with vinexin α in sensing the stiffness of the extracellular matrix. J Cell Sci 127: 1875‐1886, 2014.
 430.Yang C, Tibbitt MW, Basta L, Anseth KS. Mechanical memory and dosing influence stem cell fate. Nat Mater 13: 645‐652, 2014.
 431.Yaqoob U, Cao S, Shergill U, Jagavelu K, Geng Z, Yin M, De Assuncao TM, Cao Y, Szabolcs A, Thorgeirsson S. Neuropilin‐1 stimulates tumor growth by increasing fibronectin fibril assembly in the tumor microenvironment. Cancer Res 72: 4047‐4059, 2012.
 432.Yasmin MRA, McEniery CM, Cleary SE, Li Y, Siew K, Figg NL, Khir AW, Cockcroft JR, Wilkinson IB, O'Shaughnessy KM. The matrix proteins aggrecan and fibulin‐1 play a key role in determining aortic stiffness. Sci Rep 8: 8550, 2018.
 433.Yeh YC, Corbin EA, Caliari SR, Ouyang L, Vega SL, Truitt R, Han L, Margulies KB, Burdick JA. Mechanically dynamic PDMS substrates to investigate changing cell environments. Biomaterials 145: 23‐32, 2017.
 434.Yeh YT, Hur SS, Chang J, Wang KC, Chiu JJ, Li YS, Chien S. Matrix stiffness regulates endothelial cell proliferation through septin 9. PLoS One 7: e46889, 2012.
 435.Yin H, Ding Y, Zhai Y, Tan W, Yin X. Orthogonal programming of heterogeneous micro‐mechano‐environments and geometries in three‐dimensional bio‐stereolithography. Nat Commun 9: 4096, 2018.
 436.Yin M, Talwalkar JA, Glaser KJ, Manduca A, Grimm RC, Rossman PJ, Fidler JL, Ehman RL. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol 5: 1207‐1213.e1202, 2007.
 437.Young DA, Choi YS, Engler AJ, Christman KL. Stimulation of adipogenesis of adult adipose‐derived stem cells using substrates that mimic the stiffness of adipose tissue. Biomaterials 34: 8581‐8588, 2013.
 438.Yu OM, Miyamoto S, Brown JH. Myocardin‐related transcription factor A and Yes‐associated protein exert dual control in G protein‐coupled receptor‐ and RhoA‐mediated transcriptional regulation and cell proliferation. Mol Cell Biol 36: 39‐49, 2016.
 439.Yuan Y, Zhong W, Ma G, Zhang B, Tian H. Yes‐associated protein regulates the growth of human non‐small cell lung cancer in response to matrix stiffness. Molecul Med Rep 11: 4267‐4272, 2015.
 440.Yurke B, Turberfield AJ, Mills AP, Simmel FC, Neumann JL. A DNA‐fuelled molecular machine made of DNA. Nature 406: 605‐608, 2000.
 441.Zemel A, Rehfeldt F, Brown AE, Discher DE, Safran SA. Optimal matrix rigidity for stress fiber polarization in stem cells. Nat Phys 6: 468‐473, 2010.
 442.Zeng Y, Yi J, Wan Z, Liu K, Song P, Chau A, Wang F, Chang Z, Han W, Zheng W, Chen YH, Xiong C, Liu W. Substrate stiffness regulates B‐cell activation, proliferation, class switch, and T‐cell‐independent antibody responses in vivo. Eur J Immunol 45: 1621‐1634, 2015.
 443.Zhang H, Yousem SA, Franklin WA, Elder E, Landreneau R, Ferson P, Keenan R, Whiteside T, Levitt ML. Differentiation and programmed cell death‐related intermediate biomarkers for the development of non‐small cell lung cancer: A pilot study. Hum Pathol 29: 965‐971, 1998.
 444.Zhang S, Holmes TC, DiPersio CM, Hynes RO, Su X, Rich A. Self‐complementary oligopeptide matrices support mammalian cell attachment. Biomaterials 16: 1385‐1393, 1995.
 445.Zhang X, Chen X, Yang T, Zhang N, Dong L, Ma S, Liu X, Zhou M, Li B. The effects of different crossing‐linking conditions of genipin on type I collagen scaffolds: An in vitro evaluation. Cell Tissue Bank 15: 531‐541, 2014.
 446.Zhang X, Kim TH, Thauland TJ, Li H, Majedi FS, Ly C, Gu Z, Butte MJ, Rowat AC, Li S. Unraveling the mechanobiology of immune cells. Curr Opin Biotechnol 66: 236‐245, 2020.
 447.Zhao B, Li L, Wang L, Wang CY, Yu J, Guan KL. Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev 26: 54‐68, 2012.
 448.Zhou J, Kim HY, Davidson LA. Actomyosin stiffens the vertebrate embryo during crucial stages of elongation and neural tube closure. Development 136: 677‐688, 2009.
 449.Zhou Y, Hagood JS, Lu B, Merryman WD, Murphy‐Ullrich JE. Thy‐1‐integrin alphav beta5 interactions inhibit lung fibroblast contraction‐induced latent transforming growth factor‐beta1 activation and myofibroblast differentiation. J Biol Chem 285: 22382‐22393, 2010.
 450.Zhou Y, Horowitz JC, Naba A, Ambalavanan N, Atabai K, Balestrini J, Bitterman PB, Corley RA, Ding BS, Engler AJ, Hansen KC, Hagood JS, Kheradmand F, Lin QS, Neptune E, Niklason L, Ortiz LA, Parks WC, Tschumperlin DJ, White ES, Chapman HA, Thannickal VJ. Extracellular matrix in lung development, homeostasis and disease. Matrix Biol 73: 77‐104, 2018.
 451.Zhou Y, Huang X, Hecker L, Kurundkar D, Kurundkar A, Liu H, Jin TH, Desai L, Bernard K, Thannickal VJ. Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis. J Clin Invest 123: 1096‐1108, 2013.
 452.Zhou Z, Qu J, He L, Zhu Y, Yang SZ, Zhang F, Guo T, Peng H, Chen P, Zhou Y. Stiff matrix instigates type I collagen biogenesis by mammalian cleavage factor I complex‐mediated alternative polyadenylation. JCI Insight 5: e133972, 2020.
 453.Zhu CQ, Popova SN, Brown ER, Barsyte‐Lovejoy D, Navab R, Shih W, Li M, Lu M, Jurisica I, Penn LZ, Gullberg D, Tsao MS. Integrin alpha 11 regulates IGF2 expression in fibroblasts to enhance tumorigenicity of human non‐small‐cell lung cancer cells. Proc Natl Acad Sci U S A 104: 11754‐11759, 2007.
 454.Zhu J, Marchant RE. Design properties of hydrogel tissue‐engineering scaffolds. Expert Rev Med Devices 8: 607‐626, 2011.
 455.Zimmermann H, Wählisch F, Baier C, Westhoff M, Reuss R, Zimmermann D, Behringer M, Ehrhart F, Katsen‐Globa A, Giese C, Marx U, Sukhorukov VL, Vásquez JA, Jakob P, Shirley SG, Zimmermann U. Physical and biological properties of barium cross‐linked alginate membranes. Biomaterials 28: 1327‐1345, 2007.
 456.Ziv K, Nuhn H, Ben‐Haim Y, Sasportas LS, Kempen PJ, Niedringhaus TP, Hrynyk M, Sinclair R, Barron AE, Gambhir SS. A tunable silk‐alginate hydrogel scaffold for stem cell culture and transplantation. Biomaterials 35: 3736‐3743, 2014.
 457.Zustiak SP. The role of matrix compliance on cell responses to drugs and toxins: Towards predictive drug screening platforms. Macromol Biosci 15: 589‐599, 2015.

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How to Cite

Ting Guo, Chao He, Aida Venado, Yong Zhou. Extracellular Matrix Stiffness in Lung Health and Disease. Compr Physiol 2022, 12: 3523-3558. doi: 10.1002/cphy.c210032