Comprehensive Physiology Wiley Online Library
Home Browse Topics Latest Issue All Issues

Lung Parenchymal Mechanics

Full Article on Wiley Online Library



Abstract

The lung parenchyma comprises a large number of thin‐walled alveoli, forming an enormous surface area, which serves to maintain proper gas exchange. The alveoli are held open by the transpulmonary pressure, or prestress, which is balanced by tissues forces and alveolar surface film forces. Gas exchange efficiency is thus inextricably linked to three fundamental features of the lung: parenchymal architecture, prestress, and the mechanical properties of the parenchyma. The prestress is a key determinant of lung deformability that influences many phenomena including local ventilation, regional blood flow, tissue stiffness, smooth muscle contractility, and alveolar stability. The main pathway for stress transmission is through the extracellular matrix. Thus, the mechanical properties of the matrix play a key role both in lung function and biology. These mechanical properties in turn are determined by the constituents of the tissue, including elastin, collagen, and proteoglycans. In addition, the macroscopic mechanical properties are also influenced by the surface tension and, to some extent, the contractile state of the adherent cells. This chapter focuses on the biomechanical properties of the main constituents of the parenchyma in the presence of prestress and how these properties define normal function or change in disease. An integrated view of lung mechanics is presented and the utility of parenchymal mechanics at the bedside as well as its possible future role in lung physiology and medicine are discussed. © 2011 American Physiological Society. Compr Physiol 1:1317‐1351, 2011.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1.

(A) Stress‐strain curves of parenchymal tissue strips from a normal rat and a rat that had been treated with elastase‐mimicking pulmonary emphysema. (B) Pressure‐volume curves measured by injecting 2 ml of air starting from functional residual capacity in a normal and an elastase‐treated rat. Adapted from Ref. with permission.

Figure 2. Figure 2.

Mean and SD of dynamic lung elastance coefficient (H) as a function of positive end‐expiratory pressure (PEEP) in groups of normal and tight skin mice. *denotes significance. Adapted from Ref. with permission.

Figure 3. Figure 3.

Structure and complexity of the parenchyma at three length scales. The top panel shows a terminal bronchiole (TB) leading to an alveolar duct (AD). The bottom left is a zoom into a single air‐filled alveolus (A) with type I (E1) and type II (E2) alveolar epithelial cells covered by a thin liquid layer. The dots represent surfactant (S) molecules at the air‐liquid interface. Secretion of lamellar bodies (LB) by the E2 cell is also shown. The right panel is a schematic representation of the extracellular matrix of the alveolar septal wall with various components including amorphous elastin (El), wavy collagen (C), complex proteoglycans (PG), basement membrane (BM) and fibroblast cells (F). (Drawing by E. Bartolák‐Suki).

Figure 4. Figure 4.

(A) Structure of collagen. Top left: single alpha helix; bottom left: collagen molecule comprising a triple helix; top right: cross‐linked collagen; bottom right: schematic view of 5 molecules; with permission from Ref. . (B) Collagen network in the rat lung is wavy at low transpulmonary pressure (left) but significantly straighter at a medium inflation level (right). AE denotes alveolar entrance. Scale bar is 10 μm. Adapted from Ref. with permission.

Figure 5. Figure 5.

(A) Longitudinal sections of elastin‐rich extracellular matrix sheets stained with acid Orcein at 0% strain (top) and 30% uniaxial strain in the horizontal direction (bottom). Note the straightening and thinning of the elastin fibers with increased strain. The scale bar denotes 10 μm. With permission from Ref. . (B) Structure of elastin in the parenchyma. V, AS, and AD denote vessel, alveolar sack, and alveolar duct, respectively. The scale bar is 200 μm. Adapted with permission from Ref. .

Figure 6. Figure 6.

Proteoglycan structure on a larger scale (A) and at a smaller scale zoom‐in (B). Different colors represent various groups; for example, blue is chondroitin sulfate, red is keratan sulfate, pink spheres are hyaluronan‐binding sites. From Ref. with permission.

Figure 7. Figure 7.

Double‐label immunohistochemistry of mouse lung tissue. The blue labels type I collagen, the brown corresponds to type III collagen, and the pink is cell nucleus. It can be seen that some fibers are comprised of almost exclusively type I or type III collagen (black arrows), whereas at several locations, the two collagen types also appear to co‐localize suggesting that they mix and form composite fibers (red arrow) where the color is intermediate between blue and brown. Green arrow shows a round nucleus, whereas the blue arrow points to an elongated nucleus suggesting that the nucleus is under mechanical tension. From Ref. with permission.

Figure 8. Figure 8.

Stress‐strain curve of collagen in tendon. Nonlinearity characterized by the heel region originates from the crimp (a) unfolding with stretching. From Ref. with permission.

Figure 9. Figure 9.

Electron microscope images of ECM sheets containing both collagen and elastin at 0% (A) and 30% (B) uniaxial strain. Images were taken at 12,500×. Arrows denote collagen fibers and the white regions are elastin. Scale bar represents 0.5 μm. From Ref. with permission.

Figure 10. Figure 10.

Fluorescent images of the same alveolar region labeled for collagen in a normal rat lung. Left: before deformation; Right after 30% uniaxial stretching vertically. The black lines show alveolar walls and the red lines are their new length and orientation after stretching. The yellow arrow points to the same septal wall junction. Note the significant change in angle between the two septal walls. Scale bar denotes 100 μm. From Ref. with permission.

Figure 11. Figure 11.

Effects of the bond‐bending parameter q on the configuration of the elastic network model at 30% strain in the vertical direction. A: stiff network with bond‐bending constant q = 100. B: soft network with q = 0.01. Color is proportional to energy carried by the springs. The maximum energy values corresponding to dark red on A and B are different. From Ref. with permission.

Figure 12. Figure 12.

Schematic drawing of the connective tissue systems in the parenchyma according to the Wilson and Bachofen model showing the alveolar duct with its axial tissue fibers organized in a helical structure, as well as the septal and peripheral fibers. The heavy arrows indicate the distending action of surface tension that exerts radially outward pull on the axial fibers of the alveolar duct. Adapted from Ref. with permission.

Figure 13. Figure 13.

Images of a region of an isolated lung at successive inflation pressures. The inflation was started from the collapsed state and the bottom, middle, and top images correspond to transpulmonary pressure of approximately 25, 27, and 30 cmH2O. Dark red corresponds to collapsed regions. Notice that as inflation progresses, the pink aerated regions gradually penetrate into the atelectatic region by pulling the underlying alveoli open (Z. Hantos and B. Suki; unpublished data).

Figure 14. Figure 14.

(A) P‐V curve during the inflation of a degassed rat lung. The inset shows a magnification of a region with many local negative elastance patterns. (B) Distributions of negative elastance from 10 inflations at rates of 2.0 ml/s (triangles) and 0.5 ml/s (circles). The regression line fits to the measured distributions are shown by dashed lines. The solid lines correspond to the distributions of negative elastance from 1000 simulated inflations of an 18‐generation symmetric binary tree. (C) An example of the P‐V curve from the inflation of the model. The inset shows a magnification of a region with many local negative elastance patterns similar to those in Fig. A. The red line in the inset traces an avalanche shock. Adapted from Ref. .

Figure 15. Figure 15.

Fits of a computational model of recruitment and derecruitment in the lung (lines) to experimental measurements of respiratory elastance (symbols) in mice with various degrees of acid‐induced injury ventilated at three different PEEP levels. Elastance was measured as a function of time following a recruitment maneuver. From Ref. with permission.

Figure 16. Figure 16.

Optical sections of a normal (left) and a ventilator‐injured (right) rat lung 20 mm below the pleural surface. Because the injured lung had been perfused with a Fluorescein Dextran, alveolar edema appears white on this image. Note that some alveoli are completely filled with edema fluid, while others retain trapped gas (dark ovals). From Ref. with permission.

Figure 17. Figure 17.

Pressure‐volume curves of a canine caudal lobe containing air only, saline only, and an air‐saline mixture. Note the high initial resistance up to 10 cmH2O when air is injected into a saline‐filled lung. Adapted with permission from Ref. .

Figure 18. Figure 18.

Schematic diagram of force transmission from the level of the whole lung to single cells with various feedback mechanisms influencing ECM composition and lung mechanics. Dotted lines show external or internal influences as well as various possible feedback loops in disease states (see text for explanation). Adapted from Ref. with permission.

Figure 19. Figure 19.

Schematic representation of the stress‐strain curve in arbitrary units of a lung tissue strip during uniaxial stretch in tissue bath. The regions labeled 1, 2, and 3 correspond approximately to regions of different mechanisms contributing to the stress (see text for explanation).

Figure 20. Figure 20.

Schematic representation of the P‐V curve of a lung during inflation from the collapsed state (black solid line) to total lung capacity (TLC), deflation (dashed line) to residual volume (RV), and during breathing with tidal volume (VT) from functional residual capacity (FRC). The regions labeled 1, 2, 3, and 4 correspond approximately to regions of different mechanisms contributing to the curve (see text for explanation).



Figure 1.

(A) Stress‐strain curves of parenchymal tissue strips from a normal rat and a rat that had been treated with elastase‐mimicking pulmonary emphysema. (B) Pressure‐volume curves measured by injecting 2 ml of air starting from functional residual capacity in a normal and an elastase‐treated rat. Adapted from Ref. with permission.



Figure 2.

Mean and SD of dynamic lung elastance coefficient (H) as a function of positive end‐expiratory pressure (PEEP) in groups of normal and tight skin mice. *denotes significance. Adapted from Ref. with permission.



Figure 3.

Structure and complexity of the parenchyma at three length scales. The top panel shows a terminal bronchiole (TB) leading to an alveolar duct (AD). The bottom left is a zoom into a single air‐filled alveolus (A) with type I (E1) and type II (E2) alveolar epithelial cells covered by a thin liquid layer. The dots represent surfactant (S) molecules at the air‐liquid interface. Secretion of lamellar bodies (LB) by the E2 cell is also shown. The right panel is a schematic representation of the extracellular matrix of the alveolar septal wall with various components including amorphous elastin (El), wavy collagen (C), complex proteoglycans (PG), basement membrane (BM) and fibroblast cells (F). (Drawing by E. Bartolák‐Suki).



Figure 4.

(A) Structure of collagen. Top left: single alpha helix; bottom left: collagen molecule comprising a triple helix; top right: cross‐linked collagen; bottom right: schematic view of 5 molecules; with permission from Ref. . (B) Collagen network in the rat lung is wavy at low transpulmonary pressure (left) but significantly straighter at a medium inflation level (right). AE denotes alveolar entrance. Scale bar is 10 μm. Adapted from Ref. with permission.



Figure 5.

(A) Longitudinal sections of elastin‐rich extracellular matrix sheets stained with acid Orcein at 0% strain (top) and 30% uniaxial strain in the horizontal direction (bottom). Note the straightening and thinning of the elastin fibers with increased strain. The scale bar denotes 10 μm. With permission from Ref. . (B) Structure of elastin in the parenchyma. V, AS, and AD denote vessel, alveolar sack, and alveolar duct, respectively. The scale bar is 200 μm. Adapted with permission from Ref. .



Figure 6.

Proteoglycan structure on a larger scale (A) and at a smaller scale zoom‐in (B). Different colors represent various groups; for example, blue is chondroitin sulfate, red is keratan sulfate, pink spheres are hyaluronan‐binding sites. From Ref. with permission.



Figure 7.

Double‐label immunohistochemistry of mouse lung tissue. The blue labels type I collagen, the brown corresponds to type III collagen, and the pink is cell nucleus. It can be seen that some fibers are comprised of almost exclusively type I or type III collagen (black arrows), whereas at several locations, the two collagen types also appear to co‐localize suggesting that they mix and form composite fibers (red arrow) where the color is intermediate between blue and brown. Green arrow shows a round nucleus, whereas the blue arrow points to an elongated nucleus suggesting that the nucleus is under mechanical tension. From Ref. with permission.



Figure 8.

Stress‐strain curve of collagen in tendon. Nonlinearity characterized by the heel region originates from the crimp (a) unfolding with stretching. From Ref. with permission.



Figure 9.

Electron microscope images of ECM sheets containing both collagen and elastin at 0% (A) and 30% (B) uniaxial strain. Images were taken at 12,500×. Arrows denote collagen fibers and the white regions are elastin. Scale bar represents 0.5 μm. From Ref. with permission.



Figure 10.

Fluorescent images of the same alveolar region labeled for collagen in a normal rat lung. Left: before deformation; Right after 30% uniaxial stretching vertically. The black lines show alveolar walls and the red lines are their new length and orientation after stretching. The yellow arrow points to the same septal wall junction. Note the significant change in angle between the two septal walls. Scale bar denotes 100 μm. From Ref. with permission.



Figure 11.

Effects of the bond‐bending parameter q on the configuration of the elastic network model at 30% strain in the vertical direction. A: stiff network with bond‐bending constant q = 100. B: soft network with q = 0.01. Color is proportional to energy carried by the springs. The maximum energy values corresponding to dark red on A and B are different. From Ref. with permission.



Figure 12.

Schematic drawing of the connective tissue systems in the parenchyma according to the Wilson and Bachofen model showing the alveolar duct with its axial tissue fibers organized in a helical structure, as well as the septal and peripheral fibers. The heavy arrows indicate the distending action of surface tension that exerts radially outward pull on the axial fibers of the alveolar duct. Adapted from Ref. with permission.



Figure 13.

Images of a region of an isolated lung at successive inflation pressures. The inflation was started from the collapsed state and the bottom, middle, and top images correspond to transpulmonary pressure of approximately 25, 27, and 30 cmH2O. Dark red corresponds to collapsed regions. Notice that as inflation progresses, the pink aerated regions gradually penetrate into the atelectatic region by pulling the underlying alveoli open (Z. Hantos and B. Suki; unpublished data).



Figure 14.

(A) P‐V curve during the inflation of a degassed rat lung. The inset shows a magnification of a region with many local negative elastance patterns. (B) Distributions of negative elastance from 10 inflations at rates of 2.0 ml/s (triangles) and 0.5 ml/s (circles). The regression line fits to the measured distributions are shown by dashed lines. The solid lines correspond to the distributions of negative elastance from 1000 simulated inflations of an 18‐generation symmetric binary tree. (C) An example of the P‐V curve from the inflation of the model. The inset shows a magnification of a region with many local negative elastance patterns similar to those in Fig. A. The red line in the inset traces an avalanche shock. Adapted from Ref. .



Figure 15.

Fits of a computational model of recruitment and derecruitment in the lung (lines) to experimental measurements of respiratory elastance (symbols) in mice with various degrees of acid‐induced injury ventilated at three different PEEP levels. Elastance was measured as a function of time following a recruitment maneuver. From Ref. with permission.



Figure 16.

Optical sections of a normal (left) and a ventilator‐injured (right) rat lung 20 mm below the pleural surface. Because the injured lung had been perfused with a Fluorescein Dextran, alveolar edema appears white on this image. Note that some alveoli are completely filled with edema fluid, while others retain trapped gas (dark ovals). From Ref. with permission.



Figure 17.

Pressure‐volume curves of a canine caudal lobe containing air only, saline only, and an air‐saline mixture. Note the high initial resistance up to 10 cmH2O when air is injected into a saline‐filled lung. Adapted with permission from Ref. .



Figure 18.

Schematic diagram of force transmission from the level of the whole lung to single cells with various feedback mechanisms influencing ECM composition and lung mechanics. Dotted lines show external or internal influences as well as various possible feedback loops in disease states (see text for explanation). Adapted from Ref. with permission.



Figure 19.

Schematic representation of the stress‐strain curve in arbitrary units of a lung tissue strip during uniaxial stretch in tissue bath. The regions labeled 1, 2, and 3 correspond approximately to regions of different mechanisms contributing to the stress (see text for explanation).



Figure 20.

Schematic representation of the P‐V curve of a lung during inflation from the collapsed state (black solid line) to total lung capacity (TLC), deflation (dashed line) to residual volume (RV), and during breathing with tidal volume (VT) from functional residual capacity (FRC). The regions labeled 1, 2, 3, and 4 correspond approximately to regions of different mechanisms contributing to the curve (see text for explanation).

References
 1. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 342: 1301‐1301, 2000.
 2. Agostoni E, D'Angelo E, Bonanni MV. The effect of the abdomen on the vertical gradient of pleural surface pressure. Respir Physiol 8: 332‐332, 1970.
 3. Al Jamal R, Roughley PJ, Ludwig MS. Effect of glycosaminoglycan degradation on lung tissue viscoelasticity. Am J Physiol Lung Cell Mol Physiol 280: L306‐L315, 2001.
 4. Alencar AM, Arold SP, Buldyrev SV, Majumdar A, Stamenovic D, Stanley HE, Suki B. Physiology: Dynamic instabilities in the inflating lung. Nature 417: 809‐809, 2002.
 5. Allen GB, Leclair T, Cloutier M, Thompson‐Figueroa J, Bates JH. The response to recruitment worsens with progression of lung injury and fibrin accumulation in a mouse model of acid aspiration. Am J Physiol Lung Cell Mol Physiol 292: L1580‐1589, 2007.
 6. Allen GB, Pavone LA, DiRocco JD, Bates JH, Nieman GF. Pulmonary impedance and alveolar instability during injurious ventilation in rats. J Appl Physiol 99: 723‐723, 2005.
 7. Angele P, Abke J, Kujat R, Faltermeier H, Schumann D, Nerlich M, Kinner B, Englert C, Ruszczak Z, Mehrl R, Mueller R. Influence of different collagen species on physico‐chemical properties of crosslinked collagen matrices. Biomaterials 25: 2831‐2831, 2004.
 8. Antunes MA, Abreu SC, Damaceno‐Rodrigues NR, Parra ER, Capelozzi VL, Pinart M, Romero PV, Silva PM, Martins MA, Rocco PR. Different strains of mice present distinct lung tissue mechanics and extracellular matrix composition in a model of chronic allergic asthma. Respir Physiol Neurobiol 165: 202‐202, 2009.
 9. Arbabi S, Sahimi M. Elastic properties of three‐dimensional percolation networks with stretching and bond‐bending forces. Phys Rev B Condens Matter 38: 7173‐7173, 1988.
 10. Arold SP, Bartolak‐Suki E, Suki B. Variable stretch pattern enhances surfactant secretion in alveolar type II cells in culture. Am J Physiol Lung Cell Mol Physiol 296: L574‐581, 2009.
 11. Avery ME, Mead J. Surface properties in relation to atelectasis and hyaline membrane disease. AMA J Dis Child 97: 517‐517, 1959.
 12. Avery NC, Bailey AJ. Enzymic and non‐enzymic cross‐linking mechanisms in relation to turnover of collagen: Relevance to aging and exercise. Scand J Med Sci Sports 15: 231‐231, 2005.
 13. Azeloglu EU, Bhattacharya J, Costa KD. Atomic force microscope elastography reveals phenotypic differences in alveolar cell stiffness. J Appl Physiol 105: 652‐652, 2008.
 14. Bachofen H, Gehr P, Weibel ER. Alterations of mechanical properties and morphology in excised rabbit lungs rinsed with a detergent. J Appl Physiol 47: 1002‐1002, 1979.
 15. Bachofen H, Hildebrandt J, Bachofen M. Pressure‐volume curves of air‐ and liquid‐filled excised lungs‐surface tension in situ. J Appl Physiol 29: 422‐422, 1970.
 16. Balland M, Desprat N, Icard D, Fereol S, Asnacios A, Browaeys J, Henon S, Gallet F. Power laws in microrheology experiments on living cells: Comparative analysis and modeling. Phys Rev E Stat Nonlin Soft Matter Phys 74: 021911, 2006.
 17. Barnas GM, Stamenovic D, Fredberg JJ. Proportionality between chest wall resistance and elastance. J Appl Physiol 70: 511‐511, 1991.
 18. Bates JH. A recruitment model of quasi‐linear power‐law stress adaptation in lung tissue. Ann Biomed Eng 35: 1165‐1165, 2007.
 19. Bates JH, Davis GS, Majumdar A, Butnor KJ, Suki B. Linking parenchymal disease progression to changes in lung mechanical function by percolation. Am J Respir Crit Care Med 176: 617‐617, 2007.
 20. Bates JH, Irvin CG. Time dependence of recruitment and derecruitment in the lung: A theoretical model. J Appl Physiol 93: 705‐705, 2002.
 21. Bates JH, Maksym GN, Navajas D, Suki B. Lung tissue rheology and 1/f noise. Ann Biomed Eng 22: 674‐674, 1994.
 22. Bayliss LE, Robertson GW. The visco‐elastic properties of the lungs. Quart J Exp Physiol 29: 27‐27, 1939.
 23. Bellardine Black CL, Hoffman AM, Tsai LW, Ingenito EP, Suki B, Kaczka DW, Simon BA, Lutchen KR. Relationship between dynamic respiratory mechanics and disease heterogeneity in sheep lavage injury. Crit Care Med 35: 870‐870, 2007.
 24. Bellingham CM, Woodhouse KA, Robson P, Rothstein SJ, Keeley FW. Self‐aggregation characteristics of recombinantly expressed human elastin polypeptides. Biochim Biophys Acta 1550: 6‐6, 2001.
 25. Berry CC, Cacou C, Lee DA, Bader DL, Shelton JC. Dermal fibroblasts respond to mechanical conditioning in a strain profile dependent manner. Biorheology 40: 337‐337, 2003.
 26. Bertocchi C, Ravasio A, Bernet S, Putz G, Dietl P, Haller T. Optical measurement of surface tension in a miniaturized air‐liquid interface and its application in lung physiology. Biophys J 89: 1353‐1353, 2005.
 27. Bilek AM, Dee KC, Gaver DP III. Mechanisms of surface‐tension‐induced epithelial cell damage in a model of pulmonary airway reopening. J Appl Physiol 94: 770‐770, 2003.
 28. Black LD, Allen PG, Morris SM, Stone PJ, Suki B. Mechanical and failure properties of extracellular matrix sheets as a function of structural protein composition. Biophys J 94: 1916‐1916, 2008.
 29. Black LD, Brewer KK, Morris SM, Schreiber BM, Toselli P, Nugent MA, Suki B, Stone PJ. Effects of elastase on the mechanical and failure properties of engineered elastin‐rich matrices. J Appl Physiol 98: 1434‐1434, 2005.
 30. Breen EC. Mechanical strain increases type I collagen expression in pulmonary fibroblasts in vitro. J Appl Physiol 88: 203‐203, 2000.
 31. Brewer KK, Sakai H, Alencar AM, Majumdar A, Arold SP, Lutchen KR, Ingenito EP, Suki B. Lung and alveolar wall elastic and hysteretic behavior in rats: Effects of in vivo elastase treatment. J Appl Physiol 95: 1926‐1926, 2003.
 32. Briggs JN, Hogg G. Perinatal pulmonary pathology. Pediatrics 22: 41‐41, 1958.
 33. Brismar B, Hedenstierna G, Lundquist H, Strandberg A, Svensson L, Tokics L. Pulmonary densities during anesthesia with muscular relaxation—a proposal of atelectasis. Anesthesiology 62: 422‐422, 1985.
 34. Brown JC, Timpl R. The collagen superfamily. Int Arch Allergy Immunol 107: 484‐484, 1995.
 35. Brown RE, Butler JP, Rogers RA, Leith DE. Mechanical connections between elastin and collagen. Connect Tissue Res 30: 295‐295, 1994.
 36. Buckwalter JA, Rosenberg LC. Electron microscopic studies of cartilage proteoglycans. Direct evidence for the variable length of the chondroitin sulfate‐rich region of proteoglycan subunit core protein. J Biol Chem 257: 9830‐9830, 1982.
 37. Budiansky B, Kimmel E. Elastic moduli of lungs. J Appl Mech 54: 351‐351, 1987.
 38. Buldyrev SV. Fractals in biology. In: Meyers RA, editor. Encyclopedia of Complexity and Systems Science. New York: Springer, 2009, p. 3889‐3889.
 39. Butler JP, Miki H, Squarcia S, Rogers RA, Lehr JL. Effect of macroscopic deformation on lung microstructure. J Appl Physiol 81: 1792‐1792, 1996.
 40. Campagnone R, Regan J, Rich CB, Miller M, Keene DR, Sakai L, Foster JA. Pulmonary fibroblasts: A model system for studying elastin synthesis. Lab Invest 56: 224‐224, 1987.
 41. Carey DJ. Biological functions of proteoglycans: Use of specific inhibitors of proteoglycan synthesis. Mol Cell Biochem 104: 21‐21, 1991.
 42. Carey DJ. Syndecans: Multifunctional cell‐surface co‐receptors. Biochem J 327 (Pt 1): 1‐1, 1997.
 43. Carver W, Nagpal ML, Nachtigal M, Borg TK, Terracio L. Collagen expression in mechanically stimulated cardiac fibroblasts. Circ Res 69: 116‐116, 1991.
 44. Cassidy KJ, Halpern D, Ressler BG, Grotberg JB. Surfactant effects in model airway closure experiments. J Appl Physiol 87: 415‐415, 1999.
 45. Cavalcante FS, Ito S, Brewer KK, Sakai H, Alencar AM, Almeida MP, Andrade JS Jr, Majumdar A, Ingenito EP, Suki B. Mechanical interactions between collagen and proteoglycans: Implications for the stability of lung tissue. J Appl Physiol 98: 672‐672, 2005.
 46. Chen CS, Alonso JL, Ostuni E, Whitesides GM, Ingber DE. Cell shape provides global control of focal adhesion assembly. Biochem Biophys Res Commun 307: 355‐355, 2003.
 47. Chiquet M, Gelman L, Lutz R, Maier S. From mechanotransduction to extracellular matrix gene expression in fibroblasts. Biochim Biophys Acta 1793: 911‐911, 2009.
 48. Chiquet M, Renedo AS, Huber F, Fluck M. How do fibroblasts translate mechanical signals into changes in extracellular matrix production? Matrix Biol 22: 73‐73, 2003.
 49. Clements JA. Functions of the alveolar lining. Am Rev Respir Dis 115: 67‐67, 1977.
 50. Clements JA, Hustead RF, Johnson RP, Gribetz I. Pulmonary surface tension and alveolar stability. J Appl Physiol 16: 444‐444, 1961.
 51. Colebatch HJ, Olsen CR, Nadel JA. Effect of histamine, serotonin, and acetylcholine on the peripheral airways. J Appl Physiol 21: 217‐217, 1966.
 52. Colombelli J, Besser A, Kress H, Reynaud EG, Girard P, Caussinus E, Haselmann U, Small JV, Schwarz US, Stelzer EH. Mechanosensing in actin stress fibers revealed by a close correlation between force and protein localization. J Cell Sci 122: 1665‐1665, 2009.
 53. Coughlin MF, Suki B, Stamenovic D. Dynamic behavior of lung parenchyma in shear. J Appl Physiol 80: 1880‐1880, 1996.
 54. Cox G, Kable E, Jones A, Fraser I, Manconi F, Gorrell MD. 3‐dimensional imaging of collagen using second harmonic generation. J Struct Biol 141: 53‐53, 2003.
 55. Crandall SH. The role of damping in vibration theory. J Sound Vibr 11: 3‐3, 1970.
 56. Daamen WF, Veerkamp JH, van Hest JC, van Kuppevelt TH. Elastin as a biomaterial for tissue engineering. Biomaterials 28: 4378‐4378, 2007.
 57. Davies PF, Shi C, Depaola N, Helmke BP, Polacek DC. Hemodynamics and the focal origin of atherosclerosis: A spatial approach to endothelial structure, gene expression, and function. Ann N Y Acad Sci 947: 7‐7; discussion 16‐16, 2001.
 58. Denny E, Schroter RC. The mechanical behavior of a mammalian lung alveolar duct model. J Biomech Eng 117: 254‐254, 1995.
 59. Denny E, Schroter RC. A model of non‐uniform lung parenchyma distortion. J Biomech 39: 652‐652, 2006.
 60. Denny E, Schroter RC. Relationships between alveolar size and fibre distribution in a mammalian lung alveolar duct model. J Biomech Eng 119: 289‐289, 1997.
 61. Denny E, Schroter RC. Viscoelastic behavior of a lung alveolar duct model. J Biomech Eng 122: 143‐143, 2000.
 62. Dewey TG. Fractals in Molecular Biophysics. Oxford; New York: Oxford University Press, 1997.
 63. Discher DE, Janmey P, Wang YL. Tissue cells feel and respond to the stiffness of their substrate. Science 310: 1139‐1139, 2005.
 64. Dolhnikoff M, Mauad T, Ludwig MS. Extracellular matrix and oscillatory mechanics of rat lung parenchyma in bleomycin‐induced fibrosis. Am J Respir Crit Care Med 160: 1750‐1750, 1999.
 65. Dolhnikoff M, Morin J, Ludwig MS. Human lung parenchyma responds to contractile stimulation. Am J Respir Crit Care Med 158: 1607‐1607, 1998.
 66. Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end‐expiratory pressure. Am Rev Respir Dis 137: 1159‐1159, 1988.
 67. 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: 1569‐1569, 2000.
 68. Fabry B, Maksym GN, Butler JP, Glogauer M, Navajas D, Fredberg JJ. Scaling the microrheology of living cells. Phys Rev Lett 87: 148102, 2001.
 69. Faffe DS, Silva GH, Kurtz PM, Negri EM, Capelozzi VL, Rocco PR, Zin WA. Lung tissue mechanics and extracellular matrix composition in a murine model of silicosis. J Appl Physiol 90: 1400‐1400, 2001.
 70. Fernandez P, Pullarkat PA, Ott A. A master relation defines the nonlinear viscoelasticity of single fibroblasts. Biophys J 90: 3796‐3796, 2006.
 71. Fratzl P, Daxer A. Structural transformation of collagen fibrils in corneal stroma during drying. An x‐ray scattering study. Biophys J 64: 1210‐1210, 1993.
 72. Fratzl P, Misof K, Zizak I, Rapp G, Amenitsch H, Bernstorff S. Fibrillar structure and mechanical properties of collagen. J Struct Biol 122: 119‐119, 1998.
 73. Fredberg JJ, Bunk D, Ingenito E, Shore SA. Tissue resistance and the contractile state of lung parenchyma. J Appl Physiol 74: 1387‐1387., 1993.
 74. Fredberg JJ, Inouye D, Miller B, Nathan M, Jafari S, Raboudi SH, Butler JP, Shore SA. Airway smooth muscle, tidal stretches, and dynamically determined contractile states. Am J Respir Crit Care Med 156: 1752‐1752, 1997.
 75. Fredberg JJ, Jones KA, Nathan M, Raboudi S, Prakash YS, Shore SA, Butler JP, Sieck GC. Friction in airway smooth muscle: Mechanism, latch, and implications in asthma. J Appl Physiol 81: 2703‐2703, 1996.
 76. Fredberg JJ, Kamm RD. Stress transmission in the lung: Pathways from organ to molecule. Annu Rev Physiol 68: 507‐507, 2006.
 77. Fredberg JJ, Stamenovic D. On the imperfect elasticity of lung tissue. J Appl Physiol 67: 2408‐2408, 1989.
 78. Fredberg JJ, Wang N, Stamenovic D, Ingber DE. Micromechanics of the lung: From the parenchyma to the cytoskeleton. In: Hlastala MP, Robertson HT, editors. Complexity in Structure and Function of the Lung. New York: Dekker, 1998, p. 99‐99.
 79. Fukaya H, Martin CJ, Young AC, Katsura S. Mechanial properties of alveolar walls. J Appl Physiol 25: 689‐689, 1968.
 80. Fung YC. Does the surface tension make the lung inherently unstable? Circ Res 37: 497‐497, 1975.
 81. Fung YC. Stress, deformation, and atelectasis of the lung. Circ Res 37: 481‐481, 1975.
 82. Fung YC. A model of the lung structure and its validation. J Appl Physiol 64: 2132‐2132, 1988.
 83. Fung YC. Biomechanics: Mechanical Properties of Living Tissues. New York: Springer‐Verlag, 1993.
 84. Fust A, LeBellego F, Iozzo RV, Roughley PJ, Ludwig MS. Alterations in lung mechanics in decorin‐deficient mice. Am J Physiol Lung Cell Mol Physiol 288: L159‐L166, 2005.
 85. Gattinoni L, Presenti A, Torresin A, Baglioni S, Rivolta M, Rossi F, Scarani F, Marcolin R, Cappelletti G. Adult respiratory distress syndrome profiles by computed tomography. J Thorac Imaging 1: 25‐25, 1986.
 86. Gaver DP III, Samsel RW, Solway J. Effects of surface tension and viscosity on airway reopening. J Appl Physiol 69: 74‐74, 1990.
 87. Gefen A, Elad D, Shiner RJ. Analysis of stress distribution in the alveolar septa of normal and simulated emphysematic lungs. J Biomech 32: 891‐891, 1999.
 88. Gheduzzi D, Guerra D, Bochicchio B, Pepe A, Tamburro AM, Quaglino D, Mithieux S, Weiss AS, Pasquali Ronchetti I. Heparan sulphate interacts with tropoelastin, with some tropoelastin peptides and is present in human dermis elastic fibers. Matrix Biol 24: 15‐15, 2005.
 89. Giancotti FG, Ruoslahti E. Integrin signaling. Science 285: 1028‐1028, 1999.
 90. Gil J, Bachofen H, Gehr P, Weibel ER. Alveolar volume‐surface area relation in air‐ and saline‐filled lungs fixed by vascular perfusion. J Appl Physiol 47: 990‐990, 1979.
 91. Giraud‐Guille MM, Besseau L. Banded patterns in liquid crystalline phases of type I collagen: Relationship with crimp morphology in connective tissue architecture. Connect Tissue Res 37: 183‐183, 1998.
 92. Goerke J. Pulmonary surfactant: Functions and molecular composition. Biochim Biophys Acta 1408: 79‐79, 1998.
 93. Goldstein RH, Lucey EC, Franzblau C, Snider GL. Failure of mechanical properties to parallel changes in lung connective tissue composition in bleomycin‐induced pulmonary fibrosis in hamsters. Am Rev Respir Dis 120: 67‐67, 1979.
 94. Gomes RF, Shen X, Ramchandani R, Tepper RS, Bates JH. Comparative respiratory system mechanics in rodents. J Appl Physiol 89: 908‐908, 2000.
 95. Graves IA, Hildebrandt J, Hoppin FG Jr. Micromechanics of the lung. In: Fishman AP, editor. Handbook of Physiology. The Respiratory System. Mechanics of Breathing. Bethesda: Am Physiol Soc, 1986, p. 217‐217.
 96. Gunasekara L, Schoel WM, Schurch S, Amrein MW. A comparative study of mechanisms of surfactant inhibition. Biochim Biophys Acta 1778: 433‐433, 2008.
 97. Gutierrez JA, Perr HA. Mechanical stretch modulates TGF‐beta1 and alpha1(I) collagen expression in fetal human intestinal smooth muscle cells. Am J Physiol 277: G1074‐G1080, 1999.
 98. Hajji MA, Wilson TA, Lai‐Fook SJ. Improved measurements of shear modulus and pleural membrane tension of the lung. J Appl Physiol 47: 175‐175, 1979.
 99. Hantos Z, Adamicza A, Janosi TZ, Szabari MV, Tolnai J, Suki B. Lung volumes and respiratory mechanics in elastase‐induced emphysema in mice. J Appl Physiol 105: 1864‐1864, 2008.
 100. Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ. Input impedance and peripheral inhomogeneity of dog lungs. J Appl Physiol 72: 168‐168, 1992.
 101. Hantos Z, Suki B, Csendes T, Daroczy B. Constant‐phase modelling of pulmonary tissue impedance (Abstract). Bull Eur Physiopathol Respir 23: Suppl. 12: 326s, 1987.
 102. Hildebrandt J. Comparison of mathematical models for cat lung and viscoelastic balloon derived by Laplace transform methods from pressure‐volume data. Bull Math Biophys 31: 651‐651, 1969.
 103. Hildebrandt J. Dynamic properties of air‐filled excised cat lung determined by liquid plethysmograph. J Appl Physiol 27: 246‐246, 1969.
 104. Hildebrandt J. Pressure‐volume data of cat lung interpreted by a plastoelastic, linear viscoelastic model. J Appl Physiol 28: 365‐365, 1970.
 105. Hinz B. Tissue stiffness, latent TGF‐beta1 activation, and mechanical signal transduction: Implications for the pathogenesis and treatment of fibrosis. Curr Rheumatol Rep 11: 120‐120, 2009.
 106. Holmes DF, Gilpin CJ, Baldock C, Ziese U, Koster AJ, Kadler KE. Corneal collagen fibril structure in three dimensions: Structural insights into fibril assembly, mechanical properties, and tissue organization. Proc Natl Acad Sci U S A 98: 7307‐7307, 2001.
 107. Hoppin FG Jr, Hughes JM, Mead J. Axial forces in the bronchial tree. J Appl Physiol 42: 773‐773, 1977.
 108. Horie T, Hildebrandt J. Dynamic compliance, limit cycles, and static equilibria of excised cat lung. J Appl Physiol 31: 423‐423, 1971.
 109. Horie T, Hildebrandt J. Volume history, static equilibrium, and dynamic compliance of excised cat lung. J Appl Physiol 33: 105‐105, 1972.
 110. Houghton AM, Quintero PA, Perkins DL, Kobayashi DK, Kelley DG, Marconcini LA, Mecham RP, Senior RM, Shapiro SD. Elastin fragments drive disease progression in a murine model of emphysema. J Clin Invest 116: 753‐753, 2006.
 111. Huang KC, Lin CM, Tsao HK, Sheng YJ. The interactions between surfactants and vesicles: Dissipative particle dynamics. J Chem Phys 130: 245101, 2009.
 112. Huang R, Merrilees MJ, Braun K, Beaumont B, Lemire J, Clowes AW, Hinek A, Wight TN. Inhibition of versican synthesis by antisense alters smooth muscle cell phenotype and induces elastic fiber formation in vitro and in neointima after vessel injury. Circ Res 98: 370‐370, 2006.
 113. Hubmayr RD. Perspective on lung injury and recruitment: A skeptical look at the opening and collapse story. Am J Respir Crit Care Med 165: 1647‐1647, 2002.
 114. Hubmayr RD, Walters BJ, Chevalier PA, Rodarte JR, Olson LE. Topographical distribution of regional lung volume in anesthetized dogs. J Appl Physiol 54: 1048‐1048, 1983.
 115. Huh D, Fujioka H, Tung YC, Futai N, Paine R III, Grotberg JB, Takayama S. Acoustically detectable cellular‐level lung injury induced by fluid mechanical stresses in microfluidic airway systems. Proc Natl Acad Sci U S A 104: 18886‐18886, 2007.
 116. Huiskes R, Ruimerman R, van Lenthe GH, Janssen JD. Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature 405: 704‐704, 2000.
 117. Hukins DWL. Connective Tissue Matrix. London: Macmillan, 1984.
 118. Hulmes DJ, Wess TJ, Prockop DJ, Fratzl P. Radial packing, order, and disorder in collagen fibrils. Biophys J 68: 1661‐1661, 1995.
 119. Humphrey JD, Vawter DL, Vito RP. Pseudoelasticity of excised visceral pleura. J Biomech Eng 109: 115‐115, 1987.
 120. Ingber D. Integrins as mechanochemical transducers. Curr Opin Cell Biol 3: 841‐841, 1991.
 121. Ingber DE. Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circ Res 91: 877‐877, 2002.
 122. Ingenito EP, Mark L, Davison B. Effects of acute lung injury on dynamic tissue properties. J Appl Physiol 77: 2689‐2689, 1994.
 123. Ingenito EP, Mark L, Morris J, Espinosa FF, Kamm RD, Johnson M. Biophysical characterization and modeling of lung surfactant components. J Appl Physiol 86: 1702‐1702, 1999.
 124. Ingenito EP, Tsai LW, Mentzer SJ, Jaklitsch MT, Reilly JJ, Lutchen K, Mazan M, Hoffman A. Respiratory impedance following bronchoscopic or surgical lung volume reduction for emphysema. Respiration 72: 406‐406, 2005.
 125. Iozzo RV. Matrix proteoglycans: From molecular design to cellular function. Annu Rev Biochem 67: 609‐609, 1998.
 126. Ito S, Bartolak‐Suki E, Shipley JM, Parameswaran H, Majumdar A, Suki B. Early emphysema in the tight skin and pallid mice: Roles of microfibril‐associated glycoproteins, collagen, and mechanical forces. Am J Respir Cell Mol Biol 34: 688‐688, 2006.
 127. Ito S, Ingenito EP, Arold SP, Parameswaran H, Tgavalekos NT, Lutchen KR, Suki B. Tissue heterogeneity in the mouse lung: Effects of elastase treatment. J Appl Physiol 97: 204‐204, 2004.
 128. 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: 503‐503, 2005.
 129. Ito S, Majumdar A, Kume H, Shimokata K, Naruse K, Lutchen KR, Stamenovic D, Suki B. Viscoelastic and dynamic nonlinear properties of airway smooth muscle tissue: Roles of mechanical force and the cytoskeleton. Am J Physiol Lung Cell Mol Physiol 290: L1227‐1237, 2006.
 130. Ji L, Lim J, Danuser G. Fluctuations of intracellular forces during cell protrusion. Nat Cell Biol 10: 1393‐1393, 2008.
 131. Juul SE, Kinsella MG, Wight TN, Hodson WA. Alterations in nonhuman primate (M. nemestrina) lung proteoglycans during normal development and acute hyaline membrane disease. Am J Respir Cell Mol Biol 8: 299‐299, 1993.
 132. Kaczka DW, Hager DN, Hawley ML, Simon BA. Quantifying mechanical heterogeneity in canine acute lung injury: Impact of mean airway pressure. Anesthesiology 103: 306‐306, 2005.
 133. Kielty CM, Sherratt MJ, Shuttleworth CA. Elastic fibres. J Cell Sci 115: 2817‐2817, 2002.
 134. Kimmel E, Budiansky B. Surface tension and the dodecahedron model for lung elasticity. J Biomech Eng 112: 160‐160, 1990.
 135. Kitaoka H, Suki B. Branching design of the bronchial tree based on a diameter‐flow relationship. J Appl Physiol 82: 968‐968, 1997.
 136. Kitaoka H, Takaki R, Suki B. A three‐dimensional model of the human airway tree. J Appl Physiol 87: 2207‐2207, 1999.
 137. Kolozsvari B, Szijgyarto Z, Bai P, Gergely P, Verin A, Garcia JG, Bako E. Role of calcineurin in thrombin‐mediated endothelial cell contraction. Cytometry A 75: 405‐405, 2009.
 138. Kononov S, Brewer K, Sakai H, Cavalcante FS, Sabayanagam CR, Ingenito EP, Suki B. Roles of mechanical forces and collagen failure in the development of elastase‐induced emphysema. Am J Respir Crit Care Med 164: 1920‐1920., 2001.
 139. Kozel BA, Wachi H, Davis EC, Mecham RP. Domains in tropoelastin that mediate elastin deposition in vitro and in vivo. J Biol Chem 278: 18491‐18491, 2003.
 140. Kraynic AM. Foam flows. Ann Rev Fluid Mech 20: 325‐325, 1988.
 141. Krebs J, Pelosi P, Tsagogiorgas C, Alb M, Luecke T. Effects of positive end‐expiratory pressure on respiratory function and hemodynamics in patients with acute respiratory failure with and without intra‐abdominal hypertension: A pilot study. Crit Care 13: R160, 2009.
 142. Lai‐Fook SJ. Elastic properties of lung parenchyma: The effect of pressure‐volume hysteresis on the behavior of large blood vessels. J Biomech 12: 757‐757, 1979.
 143. Lai‐Fook SJ, Wilson TA, Hyatt RE, Rodarte JR. Elastic constants of inflated lobes of dog lungs. J Appl Physiol 40: 508‐508, 1976.
 144. Lambert CA, Soudant EP, Nusgens BV, Lapiere CM. Pretranslational regulation of extracellular matrix macromolecules and collagenase expression in fibroblasts by mechanical forces. Lab Invest 66: 444‐444, 1992.
 145. Lanir Y. Constitutive equations for the lung tissue. J Biomech Eng 105: 374‐374, 1983.
 146. Leikina E, Mertts MV, Kuznetsova N, Leikin S. Type I collagen is thermally unstable at body temperature. Proc Natl Acad Sci U S A 99: 1314‐1314, 2002.
 147. Leslie KO, Mitchell JJ, Woodcock‐Mitchell JL, Low RB. Alpha smooth muscle actin expression in developing and adult human lung. Differentiation 44: 143‐143, 1990.
 148. 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: 693‐693, 2010.
 149. Lucey EC, Goldstein RH, Stone PJ, Snider GL. Remodeling of alveolar walls after elastase treatment of hamsters. Results of elastin and collagen mRNA in situ hybridization. Am J Respir Crit Care Med 158: 555‐555, 1998.
 150. Lum H, Mitzner W. A species comparison of alveolar size and surface forces. J Appl Physiol 62: 1865‐1865, 1987.
 151. Lundblad LK, Thompson‐Figueroa J, Leclair T, Sullivan MJ, Poynter ME, Irvin CG, Bates JH. Tumor necrosis factor‐alpha overexpression in lung disease: A single cause behind a complex phenotype. Am J Respir Crit Care Med 171: 1363‐1363, 2005.
 152. Lutchen KR, Hantos Z, Petak F, Adamicza A, Suki B. Airway inhomogeneities contribute to apparent lung tissue mechanics during constriction. J Appl Physiol 80: 1841‐1841, 1996.
 153. Macklem PT. Respiratory mechanics. Annu Rev Physiol 40: 157‐157, 1978.
 154. Maksym GN, Bates JH. A distributed nonlinear model of lung tissue elasticity. J Appl Physiol 82: 32‐32, 1997.
 155. Maksym GN, Bates JH. Nonparametric block‐structured modeling of rat lung mechanics. Ann Biomed Eng 25: 1000‐1000, 1997.
 156. Maksym GN, Fredberg JJ, Bates JH. Force heterogeneity in a two‐dimensional network model of lung tissue elasticity. J Appl Physiol 85: 1223‐1223, 1998.
 157. Maksym GN, Kearney RE, Bates JH. Nonparametric block‐structured modeling of lung tissue strip mechanics. Ann Biomed Eng 26: 242‐242, 1998.
 158. Martynowicz MA, Hubmayr RD. Mechanisms of regional lung expansion in acute respiratory distress syndrome. In: Vincent J‐L, editor. Yearbook of Intensive Care and Emergency Medicine. Berlin: Springer‐Verlag, 1999, p. 252‐252.
 159. Martynowicz MA, Minor TA, Walters BJ, Hubmayr RD. Regional expansion of oleic acid‐injured lungs. Am J Respir Crit Care Med 160: 250‐250, 1999.
 160. Martynowicz MA, Walters BJ, Hubmayr RD. Mechanisms of recruitment in oleic acid‐injured lungs. J Appl Physiol 90: 1744‐1744, 2001.
 161. Massa CB, Allen GB, Bates JH. Modeling the dynamics of recruitment and derecruitment in mice with acute lung injury. J Appl Physiol 105: 1813‐1813, 2008.
 162. McAnulty RJ, Laurent GJ. Collagen synthesis and degradation in vivo. Evidence for rapid rates of collagen turnover with extensive degradation of newly synthesized collagen in tissues of the adult rat. Coll Relat Res 7: 93‐93, 1987.
 163. McGee KP, Hubmayr RD, Levin D, Ehman RL. Feasibility of quantifying the mechanical properties of lung parenchyma in a small‐animal model using (1)H magnetic resonance elastography (MRE). J Magn Reson Imaging 29: 838‐838, 2009.
 164. Mead J. Mechanical properties of lungs. Physiol Rev 41: 281‐281, 1961.
 165. Mead J, Takishima T, Leith D. Stress distribution in lungs: A model of pulmonary elasticity. J Appl Physiol 28: 596‐596., 1970.
 166. Mead J, Whittenberger JL, Radford J E.P. Surface tension as a factor in pulmonary volume‐pressure hysteresis. J Appl Physiol 10: 191‐191, 1957.
 167. Mecham RP, Madaras J, McDonald JA, Ryan U. Elastin production by cultured calf pulmonary artery endothelial cells. J Cell Physiol 116: 282‐282, 1983.
 168. Mercer RR, Crapo JD. Spatial distribution of collagen and elastin fibers in the lungs. J Appl Physiol 69: 756‐756, 1990.
 169. Mercer RR, Crapo JD. Structural changes in elastic fibers after pancreatic elastase administration in hamsters. J Appl Physiol 72: 1473‐1473, 1992.
 170. Mercer RR, Laco JM, Crapo JD. Three‐dimensional reconstruction of alveoli in the rat lung for pressure‐volume relationships. J Appl Physiol 62: 1480‐1480, 1987.
 171. Mercer RR, Russell ML, Crapo JD. Alveolar septal structure in different species. J Appl Physiol 77: 1060‐1060, 1994.
 172. Mijailovich SM, Stamenovic D, Brown R, Leith DE, Fredberg JJ. Dynamic moduli of rabbit lung tissue and pigeon ligamentum propatagiale undergoing uniaxial cyclic loading. J Appl Physiol 76: 773‐773., 1994.
 173. Mijailovich SM, Stamenovic D, Fredberg JJ. Toward a kinetic theory of connective tissue micromechanics. J Appl Physiol 74: 665‐665, 1993.
 174. Mishima M, Hirai T, Itoh H, Nakano Y, Sakai H, Muro S, Nishimura K, Oku Y, Chin K, Ohi M, Nakamura T, Bates JH, Alencar AM, Suki B. Complexity of terminal airspace geometry assessed by lung computed tomography in normal subjects and patients with chronic obstructive pulmonary disease. Proc Natl Acad Sci U S A 96: 8829‐8829, 1999.
 175. Misof K, Rapp G, Fratzl P. A new molecular model for collagen elasticity based on synchrotron X‐ray scattering evidence. Biophys J 72: 1376‐1376, 1997.
 176. Mithieux SM, Weiss AS. Elastin. Adv Protein Chem 70: 437‐437, 2005.
 177. Moretto A, Dallaire M, Romero P, Ludwig M. Effect of elastase on oscillation mechanics of lung parenchymal strips. J Appl Physiol 77: 1623‐1623, 1994.
 178. Morris SM, Thomas KM, Rich CB, Stone PJ. Degradation and repair of elastic fibers in rat lung interstitial fibroblast cultures. Anat Rec 250: 397‐397, 1998.
 179. Mount LE. The ventilation flow‐resistance and compliance of rat lungs. J Physiol Lond 127: 157‐157, 1955.
 180. Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 149: 1327‐1327, 1994.
 181. Nava S, Rubini F. Lung and chest wall mechanics in ventilated patients with end stage idiopathic pulmonary fibrosis. Thorax 54: 390‐390, 1999.
 182. Navajas D, Maksym GN, Bates JH. Dynamic viscoelastic nonlinearity of lung parenchymal tissue. J Appl Physiol 79: 348‐348., 1995.
 183. Navajas D, Moretto A, Rotger M, Nagase T, Dallaire MJ, Ludwig MS. Dynamic elastance and tissue resistance of isolated liquid‐filled rat lungs. J Appl Physiol 79: 1595‐1595, 1995.
 184. Nicholas TE, Barr HA. Control of release of surfactant phospholipids in the isolated perfused rat lung. J Appl Physiol 51: 90‐90, 1981.
 185. Noguchi A, Reddy R, Kursar JD, Parks WC, Mecham RP. Smooth muscle isoactin and elastin in fetal bovine lung. Exp Lung Res 15: 537‐537, 1989.
 186. O'Donnell MD, O'Connor CM, FitzGerald MX, Lungarella G, Cavarra E, Martorana PA. Ultrastructure of lung elastin and collagen in mouse models of spontaneous emphysema. Matrix Biol 18: 357‐357, 1999.
 187. Oldmixon EH, Carlsson K, Kuhn C III, Butler JP, Hoppin FG Jr. alpha‐Actin: Disposition, quantities, and estimated effects on lung recoil and compliance. J Appl Physiol 91: 459‐459, 2001.
 188. Oldmixon EH, Hoppin FG Jr. Comparison of amounts of collagen and elastin in pleura and parenchyma of dog lung. J Appl Physiol 56: 1383‐1383, 1984.
 189. Orsós F. [Die Geriistsysteme der Lunge und deren physiologische und pathologische Bedeutung]. Beitr Klin Tuberk 87: 568‐568, 1936.
 190. Otis DR Jr, Johnson M, Pedley TJ, Kamm RD. Role of pulmonary surfactant in airway closure: A computational study. J Appl Physiol 75: 1323‐1323, 1993.
 191. Parameswaran H, Majumdar A, Ito S, Alencar AM, Suki B. Quantitative characterization of airspace enlargement in emphysema. J Appl Physiol 100: 186‐186, 2006.
 192. Pedersen JA, Swartz MA. Mechanobiology in the third dimension. Ann Biomed Eng 33: 1469‐1469, 2005.
 193. Pelosi P, D'Andrea L, Vitale G, Pesenti A, Gattinoni L. Vertical gradient of regional lung inflation in adult respiratory distress syndrome. Am J Respir Crit Care Med 149: 8‐8, 1994.
 194. Perun ML, Gaver DP III. An experimental model investigation of the opening of a collapsed untethered pulmonary airway. J Biomech Eng 117: 245‐245, 1995.
 195. Perun ML, Gaver DP III. Interaction between airway lining fluid forces and parenchymal tethering during pulmonary airway reopening. J Appl Physiol 79: 1717‐1717, 1995.
 196. Petak F, Babik B, Hantos Z, Morel DR, Pache JC, Biton C, Suki B, Habre W. Impact of microvascular circulation on peripheral lung stability. Am J Physiol Lung Cell Mol Physiol 287: L879‐L889, 2004.
 197. Pillow JJ, Korfhagen TR, Ikegami M, Sly PD. Overexpression of TGF‐alpha increases lung tissue hysteresivity in transgenic mice. J Appl Physiol 91: 2730‐2730, 2001.
 198. Pinart M, Serrano‐Mollar A, Llatjos R, Rocco PR, Romero PV. Single and repeated bleomycin intratracheal instillations lead to different biomechanical changes in lung tissue. Respir Physiol Neurobiol 166: 41‐41, 2009.
 199. Polte TR, Eichler GS, Wang N, Ingber DE. Extracellular matrix controls myosin light chain phosphorylation and cell contractility through modulation of cell shape and cytoskeletal prestress. Am J Physiol Cell Physiol 286: C518‐C528, 2004.
 200. Possmayer F, Hall SB, Haller T, Petersen NO, Zuo YY, Bernardino de la Serna J, Postle AD, Veldhuizen RA, Orgeig S. Recent advances in alveolar biology: Some new looks at the alveolar interface. Respir Physiol Neurobiol 173 (Suppl): S55‐S64, 2010.
 201. Powell JT, Vine N, Crossman M. On the accumulation of D‐aspartate in elastin and other proteins of the ageing aorta. Atherosclerosis 97: 201‐201, 1992.
 202. Puxkandl R, Zizak I, Paris O, Keckes J, Tesch W, Bernstorff S, Purslow P, Fratzl P. Viscoelastic properties of collagen: Synchrotron radiation investigations and structural model. Philos Trans R Soc Lond B Biol Sci 357: 191‐191, 2002.
 203. Radford EP Jr. Static mechanical properties of mammalian lungs. In: Fenn WO, editor. Handbook of Physiology. Bethesda: American Physiological Society, 1964‐1965: 429‐429.
 204. Raspanti M, Alessandrini A, Ottani V, Ruggeri A. Direct visualization of collagen‐bound proteoglycans by tapping‐mode atomic force microscopy. J Struct Biol 119: 118‐118, 1997.
 205. Redaelli A, Vesentini S, Soncini M, Vena P, Mantero S, Montevecchi FM. Possible role of decorin glycosaminoglycans in fibril to fibril force transfer in relative mature tendons‐a computational study from molecular to microstructural level. J Biomech 36: 1555‐1555, 2003.
 206. Reinhardt DP, Sasaki T, Dzamba BJ, Keene DR, Chu ML, Gohring W, Timpl R, Sakai LY. Fibrillin‐1 and fibulin‐2 interact and are colocalized in some tissues. J Biol Chem 271: 19489‐19489, 1996.
 207. Rodarte JR, Hubmayr RD, Stamenovic D, Walters BJ. Regional lung strain in dogs during deflation from total lung capacity. J Appl Physiol 58: 164‐164, 1985.
 208. Romero FJ, Pastor A, Lopez J, Romero PV. A recruitment‐based rheological model for mechanical behavior of soft tissues. Biorheology 35: 17‐17, 1998.
 209. Roseman S. Reflections on glycobiology. J Biol Chem 276: 41527‐41527, 2001.
 210. Rosenblatt N, Hu S, Chen J, Wang N, Stamenovic D. Distending stress of the cytoskeleton is a key determinant of cell rheological behavior. Biochem Biophys Res Commun 321: 617‐617, 2004.
 211. Rosenbloom J, Abrams WR, Mecham R. Extracellular matrix 4: The elastic fiber. FASEB J 7: 1208‐1208, 1993.
 212. Rugonyi S, Biswas SC, Hall SB. The biophysical function of pulmonary surfactant. Respir Physiol Neurobiol 163: 244‐244, 2008.
 213. Sakai H, Ingenito EP, Mora R, Abbay S, Cavalcante FS, Lutchen KR, Suki B. Hysteresivity of the lung and tissue strip in the normal rat: Effects of heterogeneities. J Appl Physiol 91: 737‐737, 2001.
 214. Salerno FG, Dallaire M, Ludwig MS. Does the anatomic makeup of parenchymal lung strips affect oscillatory mechanics during induced constriction? J Appl Physiol 79: 66‐66, 1995.
 215. Sapoval B, Filoche M, Weibel ER. Smaller is better‐but not too small: A physical scale for the design of the mammalian pulmonary acinus. Proc Natl Acad Sci U S A 99: 10411‐10411, 2002.
 216. Sasaki N, Odajima S. Elongation mechanism of collagen fibrils and force‐strain relations of tendon at each level of structural hierarchy. J Biomech 29: 1131‐1131, 1996.
 217. Sasaki N, Odajima S. Stress‐strain curve and Young's modulus of a collagen molecule as determined by the X‐ray diffraction technique. J Biomech 29: 655‐655, 1996.
 218. Schild C, Trueb B. Mechanical stress is required for high‐level expression of connective tissue growth factor. Exp Cell Res 274: 83‐83, 2002.
 219. Schurch S, Bachofen H, Goerke J, Green F. Surface properties of rat pulmonary surfactant studied with the captive bubble method: Adsorption, hysteresis, stability. Biochim Biophys Acta 1103: 127‐127, 1992.
 220. Scott JE. Supramolecular organization of extracellular matrix glycosaminoglycans, in vitro and in the tissues. Faseb J 6: 2639‐2639, 1992.
 221. Setnikar I. [Origin and significance of the mechanical property of the lung]. Arch Fisiol 55: 349‐349, 1955.
 222. Shardonofsky FR, Capetanaki Y, Boriek AM. Desmin modulates lung elastic recoil and airway responsiveness. Am J Physiol Lung Cell Mol Physiol 290: L890‐896, 2006.
 223. Sherebrin MH, Song SH, Roach MR. Mechanical anisotropy of purified elastin from the thoracic aorta of dog and sheep. Can J Physiol Pharmacol 61: 539‐539, 1983.
 224. Sherratt MJ, Baldock C, Haston JL, Holmes DF, Jones CJ, Shuttleworth CA, Wess TJ, Kielty CM. Fibrillin microfibrils are stiff reinforcing fibres in compliant tissues. J Mol Biol 332: 183‐183, 2003.
 225. Shyy JY, Chien S. Role of integrins in endothelial mechanosensing of shear stress. Circ Res 91: 769‐769, 2002.
 226. Silver FH, Freeman JW, Seehra GP. Collagen self‐assembly and the development of tendon mechanical properties. J Biomech 36: 1529‐1529, 2003.
 227. Silver FH, Horvath I, Foran DJ. Mechanical implications of the domain structure of fiber‐forming collagens: Comparison of the molecular and fibrillar flexibilities of the alpha1‐chains found in types I‐III collagen. J Theor Biol 216: 243‐243, 2002.
 228. Sims TJ, Rasmussen LM, Oxlund H, Bailey AJ. The role of glycation cross‐links in diabetic vascular stiffening. Diabetologia 39: 946‐946, 1996.
 229. Sly PD, Collins RA, Thamrin C, Turner DJ, Hantos Z. Volume dependence of airway and tissue impedances in mice. J Appl Physiol 94: 1460‐1460., 2003.
 230. Smith JC, Butler JP, Hoppin FG Jr. Contribution of tree structures in the lung to lung elastic recoil. J Appl Physiol 57: 1422‐1422, 1984.
 231. Smith JC, Stamenovic D. Surface forces in lungs. I. Alveolar surface tension‐lung volume relationships. J Appl Physiol 60: 1341‐1341, 1986.
 232. Sobin SS, Fung YC, Tremer HM. Collagen and elastin fibers in human pulmonary alveolar walls. J Appl Physiol 64: 1659‐1659, 1988.
 233. Stamenovic D. Mechanical properties of pleural membrane. J Appl Physiol 57: 1189‐1189, 1984.
 234. Stamenovic D. Micromechanical foundations of pulmonary elasticity. Physiol Rev 70: 1117‐1117, 1990.
 235. Stamenovic D, Barnas GM. Effect of surface forces on oscillatory behavior of lungs. J Appl Physiol 79: 1578‐1578, 1995.
 236. Stamenovic D, Ingber DE. Models of cytoskeletal mechanics of adherent cells. Biomech Model Mechanobiol 1: 95‐95, 2002.
 237. Stamenovic D, Smith JC. Surface forces in lungs. II. Microstructural mechanics and lung stability. J Appl Physiol 60: 1351‐1351, 1986.
 238. Stamenovic D, Smith JC. Surface forces in lungs. III. Alveolar surface tension and elastic properties of lung parenchyma. J Appl Physiol 60: 1358‐1358, 1986.
 239. Stamenovic D, Wilson TA. Parenchymal stability. J Appl Physiol 73: 596‐596, 1992.
 240. Stamenovic D, Yager D. Elastic properties of air‐ and liquid‐filled lung parenchyma. J Appl Physiol 65: 2565‐2565, 1988.
 241. Stolz M, Raiteri R, Daniels AU, VanLandingham MR, Baschong W, Aebi U. Dynamic elastic modulus of porcine articular cartilage determined at two different levels of tissue organization by indentation‐type atomic force microscopy. Biophys J 86: 3269‐3269, 2004.
 242. Stromberg DD, Wiederhielm CA. Viscoelastic description of a collagenous tissue in simple elongation. J Appl Physiol 26: 857‐857, 1969.
 243. Stubbs SE, Hyatt RE. Effect of increased lung recoil pressure on maximal expiratory flow in normal subjects. J Appl Physiol 32: 325‐325, 1972.
 244. Sugihara T, Hildebrandt J, Martin CJ. Viscoelastic properties of alveolar wall. J Appl Physiol 33: 93‐93, 1972.
 245. Suki B. Nonlinear phenomena in respiratory mechanical measurements. J Appl Physiol 74: 2574‐2574, 1993.
 246. Suki B. Fluctuations and power laws in pulmonary physiology. Am J Respir Crit Care Med 166: 133‐133, 2002.
 247. Suki B, Barabasi AL, Hantos Z, Petak F, Stanley HE. Avalanches and power‐law behaviour in lung inflation. Nature 368: 615‐615, 1994.
 248. Suki B, Barabasi AL, Lutchen KR. Lung tissue viscoelasticity: A mathematical framework and its molecular basis. J Appl Physiol 76: 2749‐2749, 1994.
 249. Suki B, Bartolák‐Suki. Roles of mechanical forces and extracellular matrix properties in cellular signaling in the lung. In: Obradovic B, editor. Cell and Tissue Engineering. Belgrade: Akademska Misao and TMF, 2010, p. 158‐158.
 250. Suki B, Bates JH. A nonlinear viscoelastic model of lung tissue mechanics. J Appl Physiol 71: 826‐826, 1991.
 251. Suki B, Hantos Z. Viscoelastic properties of the visceral pleura and its contribution to lung impedance. Respir Physiol 90: 271‐271, 1992.
 252. Suki B, Ito S, Stamenovic D, Lutchen KR, Ingenito EP. Biomechanics of the lung parenchyma: Critical roles of collagen and mechanical forces. J Appl Physiol 98: 1892‐1892, 2005.
 253. Suki B, Lutchen KR, Ingenito EP. On the progressive nature of emphysema: Roles of proteases, inflammation, and mechanical forces. Am J Respir Crit Care Med 168: 516‐516, 2003.
 254. Suki B, Yuan H, Zhang Q, Lutchen KR. Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening. J Appl Physiol 82: 1349‐1349, 1997.
 255. Tanaka R, Al‐Jamal R, Ludwig MS. Maturational changes in extracellular matrix and lung tissue mechanics. J Appl Physiol 91: 2314‐2314, 2001.
 256. Tanaka R, Ludwig MS. Changes in viscoelastic properties of rat lung parenchymal strips with maturation. J Appl Physiol 87: 2081‐2081, 1999.
 257. Terragni PP, Rosboch G, Tealdi A, Corno E, Menaldo E, Davini O, Gandini G, Herrmann P, Mascia L, Quintel M, Slutsky AS, Gattinoni L, Ranieri VM. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 175: 160‐160, 2007.
 258. Thammanomai A, Majumdar A, Bartolak‐Suki E, Suki B. Effects of reduced tidal volume ventilation on pulmonary function in mice before and after acute lung injury. J Appl Physiol 103: 1551‐1551, 2007.
 259. Thurmond F, Trotter J. Morphology and biomechanics of the microfibrillar network of sea cucumber dermis. J Exp Biol 199: 1817‐1817, 1996.
 260. Torday JS, Sanchez‐Esteban J, Rubin LP. Paracrine mediators of mechanotransduction in lung development. Am J Med Sci 316: 205‐205, 1998.
 261. Toshima M, Ohtani Y, Ohtani O. Three‐dimensional architecture of elastin and collagen fiber networks in the human and rat lung. Arch Histol Cytol 67: 31‐31, 2004.
 262. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c‐fos m‐RNA expression in an isolated rat lung model. J Clin Invest 99: 944‐944, 1997.
 263. Trepat X, Grabulosa M, Buscemi L, Rico F, Farre R, Navajas D. Thrombin and histamine induce stiffening of alveolar epithelial cells. J Appl Physiol 98: 1567‐1567, 2005.
 264. Tschumperlin DJ, Boudreault F, Liu F. Recent advances and new opportunities in lung mechanobiology. J Biomech 43: 99‐99.
 265. Tschumperlin DJ, Margulies SS. Alveolar epithelial surface area‐volume relationship in isolated rat lungs. J Appl Physiol 86: 2026‐2026, 1999.
 266. Urry DW, Parker TM. Mechanics of elastin: Molecular mechanism of biological elasticity and its relationship to contraction. J Muscle Res Cell Motil 23: 543‐543, 2002.
 267. Vlahakis NE, Hubmayr RD. Cellular stress failure in ventilator‐injured lungs. Am J Respir Crit Care Med 171: 1328‐1328, 2005.
 268. Vlahovic G, Russell ML, Mercer RR, Crapo JD. Cellular and connective tissue changes in alveolar septal walls in emphysema. Am J Respir Crit Care Med 160: 2086‐2086., 1999.
 269. Von Neergaard K. [Neue Auffassungen über einen Grundbegriff der Atemmechanik; Die Retraktionskraft der Lunge, abhaängig von der Oberflaüchenspannung in den Alveolen]. Z Ges Exp Med 66: 373‐373, 1929.
 270. Wang N. Mechanical interactions among cytoskeletal filaments. Hypertension 32: 162‐162, 1998.
 271. Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260: 1124‐1124, 1993.
 272. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 342: 1334‐1334, 2000.
 273. Weibel E, Gil J. Bioengineering aspects of the lung. In: West JB, editor. Lung biology in health and disease; v. 3. New York: M. Dekker, 1977, p. 1‐1.
 274. Weibel ER. Morphometry of the human lung. New York: Academic Press, 1963.
 275. Weibel ER. What makes a good lung? Swiss Med Wkly 139: 375‐375, 2009.
 276. West JB. Distribution of mechanical stress in the lung, a possible factor in localisation of pulmonary disease. Lancet 1: 839‐839, 1971.
 277. Wilson TA. A continuum analysis of a two‐dimensional mechanical model of the lung parenchyma. J Appl Physiol 33: 472‐472., 1972.
 278. Wilson TA. Parenchymal mechanics at the alveolar level. Fed Proc 38: 7‐7, 1979.
 279. Wilson TA. Surface tension‐surface area curves calculated from pressure‐volume loops. J Appl Physiol 53: 1512‐1512, 1982.
 280. Wilson TA. The mechanics of lung parenchyma. In: Chang HK, Paiva M, editors. Respiratory Physiology—An Analytical Approach. New York: Dekker, 1989, p. 317‐317.
 281. Wilson TA, Bachofen H. A model for mechanical structure of the alveolar duct. J Appl Physiol 52: 1064‐1064, 1982.
 282. Wirtz HR, Dobbs LG. Calcium mobilization and exocytosis after one mechanical stretch of lung epithelial cells. Science 250: 1266‐1266, 1990.
 283. Wirtz HR, Dobbs LG. The effects of mechanical forces on lung functions. Respir Physiol 119: 1‐1, 2000.
 284. Woolcock AJ, Macklem PT, Hogg JC, Wilson NJ, Nadel JA, Frank NR, Brain J. Effect of vagal stimulation on central and peripheral airways in dogs. J Appl Physiol 26: 806‐806, 1969.
 285. Woolcock J, Macklem PT, Hogg JC, Wilson NJ. Influence of autonomic nervous system on airway resistance and elastic recoil. J Appl Physiol 26: 814‐814, 1969.
 286. Yuan H, Ingenito EP, Suki B. Dynamic properties of lung parenchyma: Mechanical contributions of fiber network and interstitial cells. J Appl Physiol 83: 1420‐1420; discussion 1418‐1418, 1997.
 287. Yuan H, Kononov S, Cavalcante FS, Lutchen KR, Ingenito EP, Suki B. Effects of collagenase and elastase on the mechanical properties of lung tissue strips. J Appl Physiol 89: 3‐3, 2000.
 288. Yuan H, Westwick DT, Ingenito EP, Lutchen KR, Suki B. Parametric and nonparametric nonlinear system identification of lung tissue strip mechanics. Ann Biomed Eng 27: 548‐548, 1999.
 289. Zhang Q, Suki B, Lutchen KR. Harmonic distortion from nonlinear systems with broadband inputs: Applications to lung mechanics. Ann Biomed Eng 23: 672‐672, 1995.
 290. Zuo YY, Veldhuizen RA, Neumann AW, Petersen NO, Possmayer F. Current perspectives in pulmonary surfactant‐inhibition, enhancement and evaluation. Biochim Biophys Acta 1778: 1947‐1947, 2008.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Béla Suki, Dimitrije Stamenović, Rolf Hubmayr. Lung Parenchymal Mechanics. Compr Physiol 2011, 1: 1317-1351. doi: 10.1002/cphy.c100033