Comprehensive Physiology Wiley Online Library

Mechanics of the Nucleus

Full Article on Wiley Online Library



Abstract

The nucleus is the distinguishing feature of eukaryotic cells. Until recently, it was often considered simply as a unique compartment containing the genetic information of the cell and associated machinery, without much attention to its structure and mechanical properties. This article provides compelling examples that illustrate how specific nuclear structures are associated with important cellular functions, and how defects in nuclear mechanics can cause a multitude of human diseases. During differentiation, embryonic stem cells modify their nuclear envelope composition and chromatin structure, resulting in stiffer nuclei that reflect decreased transcriptional plasticity. In contrast, neutrophils have evolved characteristic lobulated nuclei that increase their physical plasticity, enabling passage through narrow tissue spaces in their response to inflammation. Research on diverse cell types further demonstrates how induced nuclear deformations during cellular compression or stretch can modulate cellular function. Pathological examples of disturbed nuclear mechanics include the many diseases caused by mutations in the nuclear envelope proteins lamin A/C and associated proteins, as well as cancer cells that are often characterized by abnormal nuclear morphology. In this article, we will focus on determining the functional relationship between nuclear mechanics and cellular (dys‐)function, describing the molecular changes associated with physiological and pathological examples, the resulting defects in nuclear mechanics, and the effects on cellular function. New insights into the close relationship between nuclear mechanics and cellular organization and function will yield a better understanding of normal biology and will offer new clues into therapeutic approaches to the various diseases associated with defective nuclear mechanics. © 2011 American Physiological Society. Compr Physiol 1:783‐807, 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.

Orthoview of mouse embryo fibroblast immunofluorescently labeled for lamin B1 and imaged with a Nikon A1 confocal microscope. The micrograp shows the disk‐shaped nuclear morphology in the adherent fibroblast cultured on a fibronectin‐coated cover slip.

Figure 2. Figure 2.

Transmission electon micrograph of a hepatocyte nucleus showing the major structural elements of the nucleus. (Adapted from NUS Histonet, WWW Electronic Guide to Histology for Medicine and Dentistry, online at http://www.med.nus.edu.sg/ant/histonet/txt/tacsem/tac01.sem.html. TEM image courtesy of Dr. P. Gopalakrishnakone).

Figure 3. Figure 3.

Schematic overview of nuclear structure and nucleo‐cytoskeletal coupling. [Figure taken from ].

Figure 4. Figure 4.

Comparison of A‐type and B‐type lamins ectopically expressed in Xenopus oocyte nuclei. (A) Scanning electon micrograph of membrane arrays covered by lamin B2 filaments. (B) Transmission electon micrograph (TEM) section of an isolated oocyte nucleus expressing lamin B2. (C) Lamin A filaments. Filaments that are arranged in layered bundles are indicated by small arrows; they surround nuclear pore baskets (large arrrows). (D and E) TEM section of oocyte expressing lamin A (D) and control (E). The lamina is hardly visible in the control nuclei (E) but forms a thick electron‐dense layer in oocytes expressing lamin A (D), which leaves the nuclear pores clear (arrows). [Figure assembled from panels taken from ].

Figure 5. Figure 5.

Changes in fibroblast morphology in response to strain. Mouse subcutaneous tissue was stretched ex vivo (A and B) or maintained without stretch (D and E), subsequently fixed and stained with phalloidin (red) and the DNA stain SYTOX (green), and imaged by confocal microscopy. Panels (A) and (D) are composite projections of image stacks containing 20 optical sections taken at 1‐μm intervals. Panels (B) and (E) are projections of relevant optical sections containing the cells indicated by arrowheads in (A) and (D), respectively. Scale bars, 40 μm. (C) and (F): Outlines of the cell bodies in (B) and (E). [Figure taken from ].

Figure 6. Figure 6.

Transmission electron micrographs of condrocytes embedded in agarose constructs held unstrained (A to C) or subjected to 20% compression (D to F) reveal significant nuclear deformations in the compressed cells. All micrographs were taken at the same magnification (Scale bar = 2 μm). The direction of the applied strain is indicated by the horizontal arrow in (D) and (E) and a crossed circle in (F). [Figure taken from ].

Figure 7. Figure 7.

Overview of experimental techniques to probe nuclear mechanics. (A) Micropipette aspiration on isolated nuclei (top) or in intact cells after cytoskeletal disruption (bottom). (B) Atomic force microscopy. (C) Substrate strain. (D) Active microrheology. (E) Passive microrheology.

Figure 8. Figure 8.

Distinct differences in the deformation of the elastic nuclear lamina and the viscoelastic nuclear interior during micropipette aspiration. (A) Tracking a bleached region within GFP‐H2B‐labeled chromatin reveals chromatin flow within the pipette. (B) Deformation of the GFP‐lamin A‐labeled lamina stretched into the micropipette, showing elastic stretch of the lamina. The lightning bolt indicates photobleaching of a small nuclear region. (C) Nucleoli slowly follow chromatin toward the nuclear tip. Scale bar for (A‐C): 3 μm. (D and E). Fibroblast with nuclear lamina labeled by GFP‐lamin A before (D) and during (E) micropipette aspiration. The fluorescence gradient suggests thinning of the elastic nuclear lamina toward the tip. [Panels (AC) taken from ; panels (D and E) taken from ]

Figure 9. Figure 9.

Defects in nuclear morphology in neutrophils from blood smears of individuals with Pelger‐Huet anomaly (PHA) labeled with Wright‐Giemsa stain. (A) Normal neutrophil with lobulated nucleus. (B) Heterozygous PHA neutrophil with a bilobed nucleus, taken from the mother of the homozygous individual. (C) Heterozygous PHA neutrophil with a bilobed nucleus, taken from the father of the homozygote. (D) Homozygous PHA neutrophil showing an ovoid nucleus with chromatin clumping. Scale bar for light micrographs: 10 μm. (EG) Transmission electron micrographs of normal human neutrophil nucleus with three apparent lobes and extensive peripheral heterochromatin (E), heterozygous PHA neutrophil with a bilobed nucleus taken from the father of the homozygote (F), and ovoid nucleus from a homozygous PHA granulocyte exhibiting extensive heterochromatin redistribution (G). Scale bar for electron micrographs: 1 μm. [Figure taken from ]

Figure 10. Figure 10.

Abnormal nuclear mechanics in lamin A/C‐deficient fibroblasts. (A) Nucleus of wild‐type (Lmna+/+) fibroblast before strain (red) and during application of 22% substrate strain (yellow), revealing only minimal nuclear deformation. (B) Lamin A/C‐deficient (Lmna–/–) nucleus before strain (red) and during 19% substrate strain (yellow). Scale bars: 10 μm. (C) Nuclear strain as a function increases linearly with applied membrane strain, but is significantly larger in Lmna–/– fibroblasts. Dashed lines represent linear regression of the data for each cell type. (D) Maximal normalized nuclear strain (i.e., nuclear strain devided by the applied membrane strain) is significantly increased in Lmna–/– fibroblasts, indicating decreased nuclear stiffness. [Figure taken from ]



Figure 1.

Orthoview of mouse embryo fibroblast immunofluorescently labeled for lamin B1 and imaged with a Nikon A1 confocal microscope. The micrograp shows the disk‐shaped nuclear morphology in the adherent fibroblast cultured on a fibronectin‐coated cover slip.



Figure 2.

Transmission electon micrograph of a hepatocyte nucleus showing the major structural elements of the nucleus. (Adapted from NUS Histonet, WWW Electronic Guide to Histology for Medicine and Dentistry, online at http://www.med.nus.edu.sg/ant/histonet/txt/tacsem/tac01.sem.html. TEM image courtesy of Dr. P. Gopalakrishnakone).



Figure 3.

Schematic overview of nuclear structure and nucleo‐cytoskeletal coupling. [Figure taken from ].



Figure 4.

Comparison of A‐type and B‐type lamins ectopically expressed in Xenopus oocyte nuclei. (A) Scanning electon micrograph of membrane arrays covered by lamin B2 filaments. (B) Transmission electon micrograph (TEM) section of an isolated oocyte nucleus expressing lamin B2. (C) Lamin A filaments. Filaments that are arranged in layered bundles are indicated by small arrows; they surround nuclear pore baskets (large arrrows). (D and E) TEM section of oocyte expressing lamin A (D) and control (E). The lamina is hardly visible in the control nuclei (E) but forms a thick electron‐dense layer in oocytes expressing lamin A (D), which leaves the nuclear pores clear (arrows). [Figure assembled from panels taken from ].



Figure 5.

Changes in fibroblast morphology in response to strain. Mouse subcutaneous tissue was stretched ex vivo (A and B) or maintained without stretch (D and E), subsequently fixed and stained with phalloidin (red) and the DNA stain SYTOX (green), and imaged by confocal microscopy. Panels (A) and (D) are composite projections of image stacks containing 20 optical sections taken at 1‐μm intervals. Panels (B) and (E) are projections of relevant optical sections containing the cells indicated by arrowheads in (A) and (D), respectively. Scale bars, 40 μm. (C) and (F): Outlines of the cell bodies in (B) and (E). [Figure taken from ].



Figure 6.

Transmission electron micrographs of condrocytes embedded in agarose constructs held unstrained (A to C) or subjected to 20% compression (D to F) reveal significant nuclear deformations in the compressed cells. All micrographs were taken at the same magnification (Scale bar = 2 μm). The direction of the applied strain is indicated by the horizontal arrow in (D) and (E) and a crossed circle in (F). [Figure taken from ].



Figure 7.

Overview of experimental techniques to probe nuclear mechanics. (A) Micropipette aspiration on isolated nuclei (top) or in intact cells after cytoskeletal disruption (bottom). (B) Atomic force microscopy. (C) Substrate strain. (D) Active microrheology. (E) Passive microrheology.



Figure 8.

Distinct differences in the deformation of the elastic nuclear lamina and the viscoelastic nuclear interior during micropipette aspiration. (A) Tracking a bleached region within GFP‐H2B‐labeled chromatin reveals chromatin flow within the pipette. (B) Deformation of the GFP‐lamin A‐labeled lamina stretched into the micropipette, showing elastic stretch of the lamina. The lightning bolt indicates photobleaching of a small nuclear region. (C) Nucleoli slowly follow chromatin toward the nuclear tip. Scale bar for (A‐C): 3 μm. (D and E). Fibroblast with nuclear lamina labeled by GFP‐lamin A before (D) and during (E) micropipette aspiration. The fluorescence gradient suggests thinning of the elastic nuclear lamina toward the tip. [Panels (AC) taken from ; panels (D and E) taken from ]



Figure 9.

Defects in nuclear morphology in neutrophils from blood smears of individuals with Pelger‐Huet anomaly (PHA) labeled with Wright‐Giemsa stain. (A) Normal neutrophil with lobulated nucleus. (B) Heterozygous PHA neutrophil with a bilobed nucleus, taken from the mother of the homozygous individual. (C) Heterozygous PHA neutrophil with a bilobed nucleus, taken from the father of the homozygote. (D) Homozygous PHA neutrophil showing an ovoid nucleus with chromatin clumping. Scale bar for light micrographs: 10 μm. (EG) Transmission electron micrographs of normal human neutrophil nucleus with three apparent lobes and extensive peripheral heterochromatin (E), heterozygous PHA neutrophil with a bilobed nucleus taken from the father of the homozygote (F), and ovoid nucleus from a homozygous PHA granulocyte exhibiting extensive heterochromatin redistribution (G). Scale bar for electron micrographs: 1 μm. [Figure taken from ]



Figure 10.

Abnormal nuclear mechanics in lamin A/C‐deficient fibroblasts. (A) Nucleus of wild‐type (Lmna+/+) fibroblast before strain (red) and during application of 22% substrate strain (yellow), revealing only minimal nuclear deformation. (B) Lamin A/C‐deficient (Lmna–/–) nucleus before strain (red) and during 19% substrate strain (yellow). Scale bars: 10 μm. (C) Nuclear strain as a function increases linearly with applied membrane strain, but is significantly larger in Lmna–/– fibroblasts. Dashed lines represent linear regression of the data for each cell type. (D) Maximal normalized nuclear strain (i.e., nuclear strain devided by the applied membrane strain) is significantly increased in Lmna–/– fibroblasts, indicating decreased nuclear stiffness. [Figure taken from ]

References
 1. Aebi U, Cohn J, Buhle L, Gerace L. The nuclear lamina is a meshwork of intermediate‐type filaments. Nature 323: 560–564, 1986.
 2. Agrelo R, Setien F, Espada J, Artiga MJ, Rodriguez M, Perez‐Rosado A, Sanchez‐Aguilera A, Fraga MF, Piris MA, Esteller M. Inactivation of the lamin A/C gene by CpG island promoter hypermethylation in hematologic malignancies, and its association with poor survival in nodal diffuse large B‐cell lymphoma. J Clin Oncol 23: 3940–3947, 2005.
 3. Al‐Shali KZ, Hegele RA. Laminopathies and atherosclerosis. Arterioscler Thromb Vasc Biol 24: 1591–1595, 2004.
 4. Apel ED, Lewis RM, Grady RM, Sanes JR. Syne‐1, a dystrophin‐ and Klarsicht‐related protein associated with synaptic nuclei at the neuromuscular junction. J Biol Chem 275: 31986–31995, 2000.
 5. Bakay M, Wang Z, Melcon G, Schiltz L, Xuan J, Zhao P, Sartorelli V, Seo J, Pegoraro E, Angelini C, Shneiderman B, Escolar D, Chen YW, Winokur ST, Pachman LM, Fan C, Mandler R, Nevo Y, Gordon E, Zhu Y, Dong Y, Wang Y, Hoffman EP. Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb‐MyoD pathways in muscle regeneration. Brain 129 (Pt 4): 996–1013, 2006.
 6. Baker PB, Baba N, Boesel CP. Cardiovascular abnormalities in progeria. Case report and review of the literature. Arch Pathol Lab Med 105: 384–386, 1981.
 7. Bengtsson L, Wilson KL. Multiple and surprising new functions for emerin, a nuclear membrane protein. Curr Opin Cell Biol 16: 73–79, 2004.
 8. Bettinger BT, Gilbert DM, Amberg DC. Actin up in the nucleus. Nat Rev Mol Cell Biol 5: 410–415, 2004.
 9. Bhattacharya D, Talwar S, Mazumder A, Shivashankar GV. Spatio‐temporal plasticity in chromatin organization in mouse cell differentiation and during Drosophila embryogenesis. Biophys J 96: 3832–3839, 2009.
 10. Bibikova M, Laurent LC, Ren B, Loring JF, Fan JB. Unraveling epigenetic regulation in embryonic stem cells. Cell Stem Cell 2: 123–134, 2008.
 11. Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D. Identification of a novel X‐linked gene responsible for Emery‐Dreifuss muscular dystrophy. Nat Genet 8: 323–327, 1994.
 12. Bissell MJ, Weaver VM, Lelièvre SA, Wang F, Petersen OW, Schmeichel KL. Tissue structure, nuclear organization, and gene expression in normal and malignant breast. Cancer Res 59: 1757–1763, 1999.
 13. Blau HM, Pavlath GK, Hardeman EC, Chiu CP, Silberstein L, Webster SG, Miller SC, Webster C. Plasticity of the differentiated state. Science 230: 758–766, 1985.
 14. Boccardo F, Rubagotti A, Carmignani G, Romagnoli A, Nicolo G, Barboro P, Parodi S, Patrone E, Balbi C. Nuclear matrix proteins changes in cancerous prostate tissues and their prognostic value in clinically localized prostate cancer. Prostate 55: 259–264, 2003.
 15. Bonne G, Di Barletta MR, Varnous S, Becane HM, Hammouda EH, Merlini L, Muntoni F, Greenberg CR, Gary F, Urtizberea JA, Duboc D, Fardeau M, Toniolo D, Schwartz K. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery‐Dreifuss muscular dystrophy. Nat Genet 21: 285–288, 1999.
 16. Brodsky GL, Muntoni F, Miocic S, Sinagra G, Sewry C, Mestroni L. Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation 101: 473–476, 2000.
 17. Broers JL, Bronnenberg NM, Kuijpers HJ, Schutte B, Hutchison CJ, Ramaekers FC. Partial cleavage of A‐type lamins concurs with their total disintegration from the nuclear lamina during apoptosis. Eur J Cell Biol 81: 677–691, 2002.
 18. Broers JL, Hutchison CJ, Ramaekers FC. Laminopathies. J Pathol 204: 478–488, 2004.
 19. Broers JL, Peeters EA, Kuijpers HJ, Endert J, Bouten CV, Oomens CW, Baaijens FP, Ramaekers FC. Decreased mechanical stiffness in LMNA−/− cells is caused by defective nucleo‐cytoskeletal integrity: Implications for the development of laminopathies. Hum Mol Genet 13: 2567–2580, 2004.
 20. Broers JLV, Kuijpers HJH, Ostlund C, Worman HJ, Endert J, Ramaekers FCS. Both lamin A and lamin C mutations cause lamina instability as well as loss of internal nuclear lamin organization. Exp Cell Res 304: 582–592, 2005.
 21. Burke B, Roux KJ. Nuclei take a position: Managing nuclear location. Dev Cell 17: 587–597, 2009.
 22. Burke B, Stewart CL. Life at the edge: The nuclear envelope and human disease. Nat Rev Mol Cell Biol 3: 575–585, 2002.
 23. Bussolati G, Marchio C, Gaetano L, Lupo R, Sapino A. Pleomorphism of the nuclear envelope in breast cancer: A new approach to an old problem. J Cell Mol Med 12: 209–218, 2008.
 24. Caille N, Tardy Y, Meister JJ. Assessment of strain field in endothelial cells subjected to uniaxial deformation of their substrate. Ann Biomed Eng 26: 409–416, 1998.
 25. Caille N, Thoumine O, Tardy Y, Meister JJ. Contribution of the nucleus to the mechanical properties of endothelial cells. J Biomech 35: 177–187, 2002.
 26. Cao H, Hegele RA. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan‐type familial partial lipodystrophy. Hum Mol Genet 9: 109–112, 2000.
 27. Cenni V, Sabatelli P, Mattioli E, Marmiroli S, Capanni C, Ognibene A, Squarzoni S, Maraldi NM, Bonne G, Columbaro M, Merlini L, Lattanzi G. Lamin A N‐terminal phosphorylation is associated with myoblast activation: Impairment in Emery‐Dreifuss muscular dystrophy. J Med Genet 42: 214–220, 2005.
 28. Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG, Garg A, Hanson NB, Martin GM, Mian IS, Kennedy BK, Oshima J. LMNA mutations in atypical Werner's syndrome. Lancet 362: 440–445, 2003.
 29. Coffinier C, Chang SY, Nobumori C, Tu Y, Farber EA, Toth JI, Fong LG, Young SG. Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency. Proc Natl Acad Sci U S A 107: 5076–5081, 2010.
 30. Constantinescu D, Gray HL, Sammak PJ, Schatten GP, Csoka AB. Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation. Stem Cells 24: 177–185, 2006.
 31. Coradeghini R, Barboro P, Rubagotti A, Boccardo F, Parodi S, Carmignani G, D'Arrigo C, Patrone E, Balbi C. Differential expression of nuclear lamins in normal and cancerous prostate tissues. Oncol Rep 15: 609–613, 2006.
 32. Corso C, Parry EM, Faragher RG, Seager A, Green MH, Parry JM. Molecular cytogenetic insights into the ageing syndrome Hutchinson‐Gilford Progeria (HGPS). Cytogenet Genome Res 111: 27–33, 2005.
 33. Crisp M, Liu Q, Roux K, Rattner JB, Shanahan C, Burke B, Stahl PD, Hodzic D. Coupling of the nucleus and cytoplasm: Role of the LINC complex. J Cell Biol 172: 41–53, 2006.
 34. Csoka AB, English SB, Simkevich CP, Ginzinger DG, Butte AJ, Schatten GP, Rothman FG, Sedivy JM. Genome‐scale expression profiling of Hutchinson‐Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Aging Cell 3: 235–243, 2004.
 35. Cupesi M, Yoshioka J, Gannon J, Kudinova A, Stewart CL, Lammerding J. Attenuated hypertrophic response to pressure overload in a lamin A/C haploinsufficiency mouse. J Mol Cell Cardiol 48 (6): 1290–1297, 2010.
 36. Dahl KN, Engler AJ, Pajerowski JD, Discher DE. Power‐law rheology of isolated nuclei with deformation mapping of nuclear substructures. Biophys J 89: 2855–2864, 2005.
 37. Dahl KN, Kahn SM, Wilson KL, Discher DE. The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J Cell Sci 117: 4779–4786, 2004.
 38. Dahl KN, Kalinowski A, Pekkan K. Mechanobiology and the microcirculation: Cellular, nuclear and fluid mechanics. Microcirculation 17: 179–191, 2010.
 39. Dahl KN, Ribeiro AJ, Lammerding J. Nuclear shape, mechanics, and mechanotransduction. Circ Res 102: 1307–1318, 2008.
 40. Dahl KN, Scaffidi P, Islam MF, Yodh AG, Wilson KL, Misteli T. Distinct structural and mechanical properties of the nuclear lamina in Hutchinson‐Gilford progeria syndrome. Proc Natl Acad Sci U S A 103: 10271–10276, 2006.
 41. Davies PF. Flow‐mediated endothelial mechanotransduction. Physiol Rev 75: 519–560, 1995.
 42. De Sandre‐Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, Munnich A, Le Merrer M, Levy N. Lamin A Truncation in Hutchinson‐Gilford Progeria. Science 300: 2055, 2003.
 43. De Sandre‐Giovannoli A, Chaouch M, Kozlov S, Vallat JM, Tazir M, Kassouri N, Szepetowski P, Hammadouche T, Vandenberghe A, Stewart CL, Grid D, Levy N. Homozygous defects in LMNA, encoding lamin A/C nuclear‐envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot‐Marie‐Tooth disorder type 2) and mouse. Am J Hum Genet 70: 726–736, 2002.
 44. de Vries AH, Krenn BE, van Driel R, Subramaniam V, Kanger JS. Direct observation of nanomechanical properties of chromatin in living cells. Nano Lett 7: 1424–1427, 2007.
 45. Dechat T, Pfleghaar K, Sengupta K, Shimi T, Shumaker DK, Solimando L, Goldman RD. Nuclear lamins: Major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22: 832–853, 2008.
 46. Deguchi S, Maeda K, Ohashi T, Sato M. Flow‐induced hardening of endothelial nucleus as an intracellular stress‐bearing organelle. J Biomech 38: 1751–1759, 2005.
 47. Delbarre E, Tramier M, Coppey‐Moisan M, Gaillard C, Courvalin JC, Buendia B. The truncated prelamin A in Hutchinson‐Gilford progeria syndrome alters segregation of A‐type and B‐type lamin homopolymers. Hum Mol Genet 15: 1113–1122, 2006.
 48. Ding X, Xu R, Yu J, Xu T, Zhuang Y, Han M. SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice. Dev Cell 12: 863–872, 2007.
 49. Dreuillet C, Tillit J, Kress M, Ernoult‐Lange M. In vivo and in vitro interaction between human transcription factor MOK2 and nuclear lamin A/C. Nucleic Acids Res 30: 4634–4642, 2002.
 50. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell 126: 677–689, 2006.
 51. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Recurrent de novo point mutations in lamin A cause Hutchinson‐Gilford progeria syndrome. Nature 423: 293–298, 2003.
 52. Fan J, Beck KA. A role for the spectrin superfamily member Syne‐1 and kinesin II in cytokinesis. J Cell Sci 117: 619–629, 2004.
 53. Fatkin D, MacRae C, Sasaki T, Wolff MR, Porcu M, Frenneaux M, Atherton J, Vidaillet HJ, Jr, Spudich S, De Girolami U, Seidman JG, Seidman C, Muntoni F, Muehle G, Johnson W, McDonough B. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction‐system disease. N Engl J Med 341: 1715–1724, 1999.
 54. Favreau C, Higuet D, Courvalin JC, Buendia B. Expression of a mutant lamin A that causes Emery‐Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts. Mol Cell Biol 24: 1481–1492, 2004.
 55. Fidzianska A, Hausmanowa‐Petrusewicz I. Architectural abnormalities in muscle nuclei. Ultrastructural differences between X‐linked and autosomal dominant forms of EDMD. J Neurol Sci 210: 47–51, 2003.
 56. Fidzianska A, Toniolo D, Hausmanowa‐Petrusewicz I. Ultrastructural abnormality of sarcolemmal nuclei in Emery‐Dreifuss muscular dystrophy (EDMD). J Neurol Sci 159: 88–93, 1998.
 57. Frock RL, Kudlow BA, Evans AM, Jameson SA, Hauschka SD, Kennedy BK. Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation. Genes Dev 20: 486–500, 2006.
 58. Gieni RS, Hendzel MJ. Actin dynamics and functions in the interphase nucleus: Moving toward an understanding of nuclear polymeric actin. Biochem Cell Biol 87: 283–306, 2009.
 59. Gilchrist CL, Witvoet‐Braam SW, Guilak F, Setton LA. Measurement of intracellular strain on deformable substrates with texture correlation. J Biomech 40: 786–794, 2007.
 60. Goldberg MW, Fiserova J, Huttenlauch I, Stick R. A new model for nuclear lamina organization. Biochem Soc Trans 36: 1339–1343, 2008.
 61. Goldberg MW, Huttenlauch I, Hutchison CJ, Stick R. Filaments made from A‐ and B‐type lamins differ in structure and organization. J Cell Sci 121: 215–225, 2008.
 62. Gonzalez JM, Navarro‐Puche A, Casar B, Crespo P, Andres V. Fast regulation of AP‐1 activity through interaction of lamin A/C, ERK1/2, and c‐Fos at the nuclear envelope. J Cell Biol 183: 653–666, 2008.
 63. Gotic I, Schmidt WM, Biadasiewicz K, Leschnik M, Spilka R, Braun J, Stewart CL, Foisner R. Loss of LAP2 alpha delays satellite cell differentiation and affects postnatal fiber‐type determination. Stem Cells 28: 480–488, 2010.
 64. Grady RM, Starr DA, Ackerman GL, Sanes JR, Han M. Syne proteins anchor muscle nuclei at the neuromuscular junction. Proc Natl Acad Sci U S A 102: 4359–4364, 2005.
 65. Gros‐Louis F, Dupre N, Dion P, Fox MA, Laurent S, Verreault S, Sanes JR, Bouchard JP, Rouleau GA. Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia. Nat Genet 39: 80–85, 2007.
 66. Guilak F. Compression‐induced changes in the shape and volume of the chondrocyte nucleus. J Biomech 28: 1529–1541, 1995.
 67. Guilak F, Tedrow JR, Burgkart R. Viscoelastic properties of the cell nucleus. Biochem Biophys Res Commun 269: 781–786, 2000.
 68. Hahn C, Schwartz MA. Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10: 53–62, 2009.
 69. Hale CM, Shrestha AL, Khatau SB, Stewart‐Hutchinson PJ, Hernandez L, Stewart CL, Hodzic D, Wirtz D. Dysfunctional connections between the nucleus and the actin and microtubule networks in laminopathic models. Biophys J 95: 5462–5475, 2008.
 70. Haque F, Lloyd DJ, Smallwood DT, Dent CL, Shanahan CM, Fry AM, Trembath RC, Shackleton S. SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton. Mol Cell Biol 26: 3738–3751, 2006.
 71. Haque F, Mazzeo D, Patel JT, Smallwood DT, Ellis JA, Shanahan CM, Shackleton S. Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes. J Biol Chem 285: 3487–3498, 2010.
 72. Haraguchi T, Holaska JM, Yamane M, Koujin T, Hashiguchi N, Mori C, Wilson KL, Hiraoka Y. Emerin binding to Btf, a death‐promoting transcriptional repressor, is disrupted by a missense mutation that causes Emery‐Dreifuss muscular dystrophy. Eur J Biochem 271: 1035–1045, 2004.
 73. Haraguchi T, Koujin T, Segura‐Totten M, Lee KK, Matsuoka Y, Yoneda Y, Wilson KL, Hiraoka Y. BAF is required for emerin assembly into the reforming nuclear envelope. J Cell Sci 114: 4575–4585, 2001.
 74. Harborth J, Elbashir SM, Bechert K, Tuschl T, Weber K. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J Cell Sci 114: 4557–4565, 2001.
 75. Hasan S, Guttinger S, Muhlhausser P, Anderegg F, Burgler S, Kutay U. Nuclear envelope localization of human UNC84A does not require nuclear lamins. FEBS Lett 580: 1263–1268, 2006.
 76. Hazel AL, Pedley TJ. Vascular endothelial cells minimize the total force on their nuclei. Biophys J 78: 47–54, 2000.
 77. Hegele RA, Cao H, Liu DM, Costain GA, Charlton‐Menys V, Rodger NW, Durrington PN. Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet 79: 383–389, 2006.
 78. Hodzic DM, Yeater DB, Bengtsson L, Otto H, Stahl PD. Sun2 is a novel mammalian inner nuclear membrane protein. J Biol Chem 279: 25805–25812, 2004.
 79. Hoffman RM. Real‐time subcellular imaging in live animals: New visible targets for cancer drug discovery. IDrugs 9: 632–635, 2006.
 80. Hoffmann K, Dreger CK, Olins AL, Olins DE, Shultz LD, Lucke B, Karl H, Kaps R, Muller D, Vaya A, Aznar J, Ware RE, Sotelo Cruz N, Lindner TH, Herrmann H, Reis A, Sperling K. Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger‐Huet anomaly). Nat Genet 31: 410–414, 2002.
 81. Hoffmann K, Sperling K, Olins AL, Olins DE. The granulocyte nucleus and lamin B receptor: Avoiding the ovoid. Chromosoma 116: 227–235, 2007.
 82. Hofmann WA, Johnson T, Klapczynski M, Fan JL, Lanerolle P. From transcription to transport: Emerging roles for nuclear myosin I. Biochem Cell Biol 84: 418–426, 2006.
 83. Holaska JM. Emerin and the nuclear lamina in muscle and cardiac disease. Circ Res 103: 16–23, 2008.
 84. Holaska JM, Kowalski AK, Wilson KL. Emerin caps the pointed end of actin filaments: Evidence for an actin cortical network at the nuclear inner membrane. PLoS Biol 2: E231, 2004.
 85. Holaska JM, Lee KK, Kowalski AK, Wilson KL. Transcriptional repressor germ cell‐less (GCL) and barrier to autointegration factor (BAF) compete for binding to emerin in vitro. J Biol Chem 278: 6969–6975, 2003.
 86. Holaska JM, Wilson KL. An emerin “proteome”: Purification of distinct emerin‐containing complexes from HeLa cells suggests molecular basis for diverse roles including gene regulation, mRNA splicing, signaling, mechanosensing, and nuclear architecture. Biochemistry 46: 8897–8908, 2007.
 87. Hoshiba T, Yamada T, Lu H, Kawazoe N, Tateishi T, Chen G. Nuclear deformation and expression change of cartilaginous genes during in vitro expansion of chondrocytes. Biochem Biophys Res Commun 374: 688–692, 2008.
 88. Houben F, Willems CH, Declercq IL, Hochstenbach K, Kamps MA, Snoeckx LH, Ramaekers FC, Broers JL. Disturbed nuclear orientation and cellular migration in A‐type lamin deficient cells. Biochim Biophys Acta 1793: 312–324, 2009.
 89. Hu S, Chen J, Butler JP, Wang N. Prestress mediates force propagation into the nucleus. Biochem Biophys Res Commun 329: 423–428, 2005.
 90. Hudson ME, Pozdnyakova I, Haines K, Mor G, Snyder M. Identification of differentially expressed proteins in ovarian cancer using high‐density protein microarrays. Proc Natl Acad Sci U S A 104: 17494–17499, 2007.
 91. Hutchison CJ. Lamins: Building blocks or regulators of gene expression? Nat Rev Mol Cell Biol 3: 848–858, 2002.
 92. Hutchison CJ, Worman HJ. A‐type lamins: Guardians of the soma? Nat Cell Biol 6: 1062–1067, 2004.
 93. Jean RP, Gray DS, Spector AA, Chen CS. Characterization of the nuclear deformation caused by changes in endothelial cell shape. J Biomech Eng 126: 552–558, 2004.
 94. Ji JY, Lee RT, Vergnes L, Fong LG, Stewart CL, Reue K, Young SG, Zhang Q, Shanahan CM, Lammerding J. Cell nuclei spin in the absence of lamin B1. J Biol Chem 282: 20015–20026, 2007.
 95. Jockusch BM, Schoenenberger CA, Stetefeld J, Aebi U. Tracking down the different forms of nuclear actin. Trends Cell Biol 16: 391–396, 2006.
 96. Johnson BR, Nitta RT, Frock RL, Mounkes L, Barbie DA, Stewart CL, Harlow E, Kennedy BK. A‐type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc Natl Acad Sci U S A 101: 9677–9682, 2004.
 97. Kha HN, Chen BK, Clark GM, Jones R. Stiffness properties for Nucleus standard straight and contour electrode arrays. Med Eng Phys 26: 677–685, 2004.
 98. Khatau SB, Hale CM, Stewart‐Hutchinson PJ, Patel MS, Stewart CL, Searson PC, Hodzic D, Wirtz D. A perinuclear actin cap regulates nuclear shape. Proc Natl Acad Sci U S A 106: 19017–19022, 2009.
 99. Kirschner J, Brune T, Wehnert M, Denecke J, Wasner C, Feuer A, Marquardt T, Ketelsen UP, Wieacker P, Bonnemann CG, Korinthenberg R. p.S143F mutation in lamin A/C: A new phenotype combining myopathy and progeria. Ann Neurol 57: 148–151, 2005.
 100. Kiseleva E, Drummond SP, Goldberg MW, Rutherford SA, Allen TD, Wilson KL. Actin‐ and protein‐4.1‐containing filaments link nuclear pore complexes to subnuclear organelles in Xenopus oocyte nuclei. J Cell Sci 117: 2481–2490, 2004.
 101. Krauss SW, Chen C, Penman S, Heald R. Nuclear actin and protein 4.1: Essential interactions during nuclear assembly in vitro. Proc Natl Acad Sci U S A 100: 10752–10757, 2003.
 102. Kumaran RI, Muralikrishna B, Parnaik VK. Lamin A/C speckles mediate spatial organization of splicing factor compartments and RNA polymerase II transcription. J Cell Biol 159: 783–793, 2002.
 103. Lammerding J, Dahl KN, Discher DE, Kamm RD. Nuclear mechanics and methods. Methods Cell Biol 83: 269–294, 2007.
 104. Lammerding J, Fong LG, Ji JY, Reue K, Stewart CL, Young SG, Lee RT. Lamins A and C but not lamin B1 regulate nuclear mechanics. J Biol Chem 281: 25768–25780, 2006.
 105. Lammerding J, Hsiao J, Schulze PC, Kozlov S, Stewart CL, Lee RT. Abnormal nuclear shape and impaired mechanotransduction in emerin‐deficient cells. J Cell Biol 170: 781–791, 2005.
 106. Lammerding J, Schulze PC, Takahashi T, Kozlov S, Sullivan T, Kamm RD, Stewart CL, Lee RT. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest 113: 370–378, 2004.
 107. Langevin HM, Bouffard NA, Badger GJ, Churchill DL, Howe AK. Subcutaneous tissue fibroblast cytoskeletal remodeling induced by acupuncture: Evidence for a mechanotransduction‐based mechanism. J Cell Physiol 207: 767–774, 2006.
 108. Langevin HM, Bouffard NA, Badger GJ, Iatridis JC, Howe AK. Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo and in vivo. Am J Physiol Cell Physiol 288: C747–C756, 2005.
 109. Lee DA, Knight MM, Bolton JF, Idowu BD, Kayser MV, Bader DL. Chondrocyte deformation within compressed agarose constructs at the cellular and sub‐cellular levels. J Biomech 33: 81–95, 2000.
 110. Lee JS, Hale CM, Panorchan P, Khatau SB, George JP, Tseng Y, Stewart CL, Hodzic D, Wirtz D. Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration. Biophys J 93: 2542–2552, 2007.
 111. Lelièvre SA, Weaver VM, Nickerson JA, Larabell CA, Bhaumik A, Petersen OW, Bissell MJ. Tissue phenotype depends on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus. Proc Natl Acad Sci U S A 95: 14711–14716, 1998.
 112. Leman ES, Getzenberg RH. Nuclear matrix proteins as biomarkers in prostate cancer. J Cell Biochem 86: 213–223, 2002.
 113. Libotte T, Zaim H, Abraham S, Padmakumar VC, Schneider M, Lu W, Munck M, Hutchison C, Wehnert M, Fahrenkrog B, Sauder U, Aebi U, Noegel AA, Karakesisoglou I. Lamin A/C‐dependent localization of Nesprin‐2, a giant scaffolder at the nuclear envelope. Mol Biol Cell 16: 3411–3424, 2005.
 114. Lieberman‐Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J. Comprehensive mapping of long‐range interactions reveals folding principles of the human genome. Science 326: 289–293, 2009.
 115. Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadinanos J, Lopez‐Otin C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z. Genomic instability in laminopathy‐based premature aging. Nat Med 11: 780–785, 2005.
 116. Liu Q, Pante N, Misteli T, Elsagga M, Crisp M, Hodzic D, Burke B, Roux KJ. Functional association of Sun1 with nuclear pore complexes. J Cell Biol 178: 785–798, 2007.
 117. Lloyd DJ, Trembath RC, Shackleton S. A novel interaction between lamin A and SREBP1: Implications for partial lipodystrophy and other laminopathies. Hum Mol Genet 11: 769–777, 2002.
 118. Maniotis AJ, Chen CS, Ingber DE. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci U S A 94: 849–854, 1997.
 119. Markiewicz E, Ledran M, Hutchison CJ. Remodelling of the nuclear lamina and nucleoskeleton is required for skeletal muscle differentiation in vitro. J Cell Sci 118: 409–420, 2005.
 120. Mathur AB, Reichert WM, Truskey GA. Flow and high affinity binding affect the elastic modulus of the nucleus, cell body and the stress fibers of endothelial cells. Ann Biomed Eng 35: 1120–1130, 2007.
 121. Meaburn KJ, Misteli T. Cell biology: Chromosome territories. Nature 445: 379–781, 2007.
 122. Mejat A, Decostre V, Li J, Renou L, Kesari A, Hantai D, Stewart CL, Xiao X, Hoffman E, Bonne G, Misteli T. Lamin A/C‐mediated neuromuscular junction defects in Emery‐Dreifuss muscular dystrophy. J Cell Biol 184: 31–44, 2009.
 123. Melcon G, Kozlov S, Cutler DA, Sullivan T, Hernandez L, Zhao P, Mitchell S, Nader G, Bakay M, Rottman JN, Hoffman EP, Stewart CL. Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration. Hum Mol Genet 15: 637–651, 2006.
 124. Meshorer E, Gruenbaum Y. Gone with the Wnt/Notch: Stem cells in laminopathies, progeria, and aging. J Cell Biol 181: 9–13, 2008.
 125. Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell 10: 105–116, 2006.
 126. Mislow JM, Holaska JM, Kim MS, Lee KK, Segura‐Totten M, Wilson KL, McNally EM. Nesprin‐1alpha self‐associates and binds directly to emerin and lamin A in vitro. FEBS Lett 525: 135–140, 2002.
 127. Moir RD, Yoon M, Khuon S, Goldman RD. Nuclear lamins A and B1: Different pathways of assembly during nuclear envelope formation in living cells. J Cell Biol 151: 1155–1168, 2000.
 128. Mounkes LC, Stewart CL. Aging and nuclear organization: Lamins and progeria. Curr Opin Cell Biol 16: 322–327, 2004.
 129. Muchir A, Bonne G, Van Der Kooi AJ, van Meegen M, Baas F, Bolhuis PA, de Visser M, Schwartz K. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum Mol Genet 9: 1453–1459, 2000.
 130. Münter S, Enninga J, Vazquez‐Martinez R, Delbarre E, David‐Watine B, Nehrbass U, Shorte SL. Actin polymerisation at the cytoplasmic face of eukaryotic nuclei. BMC Cell Biol 7: 23, 2006.
 131. Naetar N, Korbei B, Kozlov S, Kerenyi MA, Dorner D, Kral R, Gotic I, Fuchs P, Cohen TV, Bittner R, Stewart CL, Foisner R. Loss of nucleoplasmic LAP2alpha‐lamin A complexes causes erythroid and epidermal progenitor hyperproliferation. Nat Cell Biol 10: 1341–1348, 2008.
 132. Nagano A, Koga R, Ogawa M, Kurano Y, Kawada J, Okada R, Hayashi YK, Tsukahara T, Arahata K. Emerin deficiency at the nuclear membrane in patients with Emery‐Dreifuss muscular dystrophy. Nat Genet 12: 254–259, 1996.
 133. Newport JW, Wilson KL, Dunphy WG. A lamin‐independent pathway for nuclear envelope assembly. J Cell Biol 111: 2247–2259, 1990.
 134. Nikolova V, Leimena C, McMahon AC, Tan JC, Chandar S, Jogia D, Kesteven SH, Michalicek J, Otway R, Verheyen F, Rainer S, Stewart CL, Martin D, Feneley MP, Fatkin D. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C‐deficient mice. J Clin Invest 113: 357–369, 2004.
 135. Novelli G, Muchir A, Sangiuolo F, Helbling‐Leclerc A, D'Apice MR, Massart C, Capon F, Sbraccia P, Federici M, Lauro R, Tudisco C, Pallotta R, Scarano G, Dallapiccola B, Merlini L, Bonne G. Mandibuloacral dysplasia is caused by a mutation in LMNA‐encoding lamin A/C. Am J Hum Genet 71: 426–431, 2002.
 136. Olins AL, Herrmann H, Lichter P, Kratzmeier M, Doenecke D, Olins DE. Nuclear envelope and chromatin compositional differences comparing undifferentiated and retinoic acid‐ and phorbol ester‐treated HL‐60 cells. Exp Cell Res 268: 115–127, 2001.
 137. Olins AL, Hoang TV, Zwerger M, Herrmann H, Zentgraf H, Noegel AA, Karakesisoglou I, Hodzic D, Olins DE. The LINC‐less granulocyte nucleus. Eur J Cell Biol 88: 203–214, 2009.
 138. Olins AL, Zwerger M, Herrmann H, Zentgraf H, Simon AJ, Monestier M, Olins DE. The human granulocyte nucleus: Unusual nuclear envelope and heterochromatin composition. Eur J Cell Biol 87: 279–290, 2008.
 139. Ostlund C, Folker ES, Choi JC, Gomes ER, Gundersen GG, Worman HJ. Dynamics and molecular interactions of linker of nucleoskeleton and cytoskeleton (LINC) complex proteins. J Cell Sci 122: 4099–4108, 2009.
 140. Ozaki T, Saijo M, Murakami K, Enomoto H, Taya Y, Sakiyama S. Complex formation between lamin A and the retinoblastoma gene product: Identification of the domain on lamin A required for its interaction. Oncogene 9: 2649–2653, 1994.
 141. Padiath QS, Saigoh K, Schiffmann R, Asahara H, Yamada T, Koeppen A, Hogan K, Ptacek LJ, Fu YH. Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet 38: 1114–1123, 2006.
 142. Padmakumar VC, Abraham S, Braune S, Noegel AA, Tunggal B, Karakesisoglou I, Korenbaum E. Enaptin, a giant actin‐binding protein, is an element of the nuclear membrane and the actin cytoskeleton. Exp Cell Res 295: 330–339, 2004.
 143. Padmakumar VC, Libotte T, Lu W, Zaim H, Abraham S, Noegel AA, Gotzmann J, Foisner R, Karakesisoglou I. The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin‐2 to the nuclear envelope. J Cell Sci 118: 3419–3430, 2005.
 144. Pajerowski JD, Dahl KN, Zhong FL, Sammak PJ, Discher DE. Physical plasticity of the nucleus in stem cell differentiation. Proc Natl Acad Sci U S A 104: 15619–15624, 2007.
 145. Paradisi M, McClintock D, Boguslavsky RL, Pedicelli C, Worman HJ, Djabali K. Dermal fibroblasts in Hutchinson‐Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress. BMC Cell Biol 6: 27, 2005.
 146. Pare GC, Easlick JL, Mislow JM, McNally EM, Kapiloff MS. Nesprin‐1alpha contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope. Exp Cell Res 303: 388–399, 2005.
 147. Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, Reinhart‐King CA, Margulies SS, Dembo M, Boettiger D, Hammer DA, Weaver VM. Tensional homeostasis and the malignant phenotype. Cancer Cell 8: 241–254, 2005.
 148. Pederson T. As functional nuclear actin comes into view, is it globular, filamentous, or both? J Cell Biol 180: 1061–1064, 2008.
 149. Pederson T, Aebi U. Actin in the nucleus: What form and what for? J Struct Biol 140: 3–9, 2002.
 150. Pederson T, Aebi U. Nuclear actin extends, with no contraction in sight. Mol Biol Cell 16: 5055–5060, 2005.
 151. Percipalle P, Visa N. Molecular functions of nuclear actin in transcription. J Cell Biol 172: 967–971, 2006.
 152. Philip JT, Dahl KN. Nuclear mechanotransduction: Response of the lamina to extracellular stress with implications in aging. J Biomech 41: 3164–3170, 2008.
 153. Prokocimer M, Margalit A, Gruenbaum Y. The nuclear lamina and its proposed roles in tumorigenesis: Projection on the hematologic malignancies and future targeted therapy. J Struct Biol 155: 351–360, 2006.
 154. Puckelwartz MJ, Kessler E, Zhang Y, Hodzic D, Randles KN, Morris G, Earley JU, Hadhazy M, Holaska JM, Mewborn SK, Pytel P, McNally EM. Disruption of nesprin‐1 produces an Emery Dreifuss muscular dystrophy‐like phenotype in mice. Hum Mol Genet 18: 607–620, 2009.
 155. Rosenberg‐Hasson Y, Renert‐Pasca M, Volk T. A Drosophila dystrophin‐related protein, MSP‐300, is required for embryonic muscle morphogenesis. Mech Dev 60: 83–94, 1996.
 156. Roux KJ, Crisp ML, Liu Q, Kim D, Kozlov S, Stewart CL, Burke B. Nesprin 4 is an outer nuclear membrane protein that can induce kinesin‐mediated cell polarization. Proc Natl Acad Sci U S A 106: 2194–2199, 2009.
 157. Rowat A, Foster L, Nielsen M, Weiss M, Ipsen J. Characterization of the elastic properties of the nuclear envelope. J Roy Soc Interface 2: 63–69, 2005.
 158. Rowat AC, Lammerding J, Herrmann H, Aebi U. Towards an integrated understanding of the structure and mechanics of the cell nucleus. Bioessays 30: 226–236, 2008.
 159. Rowat AC, Lammerding J, Ipsen JH. Mechanical properties of the cell nucleus and the effect of emerin deficiency. Biophys J 91: 4649–4664, 2006.
 160. Sakaki M, Koike H, Takahashi N, Sasagawa N, Tomioka S, Arahata K, Ishiura S. Interaction between emerin and nuclear lamins. J Biochem (Tokyo) 129: 321–327, 2001.
 161. Salpingidou G, Smertenko A, Hausmanowa‐Petrucewicz I, Hussey PJ, Hutchison CJ. A novel role for the nuclear membrane protein emerin in association of the centrosome to the outer nuclear membrane. J Cell Biol 178: 897–904, 2007.
 162. Schape J, Prausse S, Radmacher M, Stick R. Influence of lamin A on the mechanical properties of amphibian oocyte nuclei measured by atomic force microscopy. Biophys J 96: 4319–4325, 2009.
 163. Schirmer EC, Florens L, Guan T, Yates JR III, Gerace L. Nuclear membrane proteins with potential disease links found by subtractive proteomics. Science 301: 1380–1382, 2003.
 164. Schirmer EC, Gerace L. The stability of the nuclear lamina polymer changes with the composition of lamin subtypes according to their individual binding strengths. J Biol Chem 279: 42811–42817, 2004.
 165. Schmitt J, Benavente R, Hodzic D, Hoog C, Stewart CL, Alsheimer M. Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres to the nuclear envelope. Proc Natl Acad Sci U S A 104: 7426–7431, 2007.
 166. Schoenenberger CA, Buchmeier S, Boerries M, Sütterlin R, Aebi U, Jockusch BM. Conformation‐specific antibodies reveal distinct actin structures in the nucleus and the cytoplasm. J Struct Biol 152: 157–168, 2005.
 167. Shackleton S, Lloyd DJ, Jackson SN, Evans R, Niermeijer MF, Singh BM, Schmidt H, Brabant G, Kumar S, Durrington PN, Gregory S, O'Rahilly S, Trembath RC. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet 24: 153–156, 2000.
 168. Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, Goldman AE, Adam SA, Shumaker DK, Kinjo M, Cremer T, Goldman RD. The A‐ and B‐type nuclear lamin networks: Microdomains involved in chromatin organization and transcription. Genes Dev 22: 3409–3421, 2008.
 169. Sjakste N, Sjakste T, Vikmanis U. Role of the nuclear matrix proteins in malignant transformation and cancer diagnosis. Exp Oncol 26: 170–178, 2004.
 170. Spann TP, Goldman AE, Wang C, Huang S, Goldman RD. Alteration of nuclear lamin organization inhibits RNA polymerase II‐dependent transcription. J Cell Biol 156: 603–608, 2002.
 171. Spencer VA, Samuel SK, Davie JR. Altered profiles in nuclear matrix proteins associated with DNA in situ during progression of breast cancer cells. Cancer Res 61: 1362–1366, 2001.
 172. Starr DA, Han M. Role of ANC‐1 in tethering nuclei to the actin cytoskeleton. Science 298: 406–409, 2002.
 173. Stehbens WE, Delahunt B, Shozawa T, Gilbert‐Barness E. Smooth muscle cell depletion and collagen types in progeric arteries. Cardiovasc Pathol 10: 133–136, 2001.
 174. Stehbens WE, Wakefield SJ, Gilbert‐Barness E, Olson RE, Ackerman J. Histological and ultrastructural features of atherosclerosis in progeria. Cardiovasc Pathol 8: 29–39, 1999.
 175. Stewart C, Burke B. Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B. Cell 51: 383–392, 1987.
 176. Storch KN, Taatjes DJ, Bouffard NA, Locknar S, Bishop NM, Langevin HM. Alpha smooth muscle actin distribution in cytoplasm and nuclear invaginations of connective tissue fibroblasts. Histochem Cell Biol 127: 523–530, 2007.
 177. Sullivan T, Escalante‐Alcalde D, Bhatt H, Anver M, Bhat N, Nagashima K, Stewart CL, Burke B. Loss of A‐type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol 147: 913–920, 1999.
 178. Tang CW, Maya‐Mendoza A, Martin C, Zeng K, Chen S, Feret D, Wilson SA, Jackson DA. The integrity of a lamin‐B1‐dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells. J Cell Sci 121: 1014–1024, 2008.
 179. Theret DP, Levesque MJ, Sato M, Nerem RM, Wheeler LT. The application of a homogeneous half‐space model in the analysis of endothelial cell micropipette measurements. J Biomech Eng 110: 190–199, 1988.
 180. Thomas CH, Collier JH, Sfeir CS, Healy KE. Engineering gene expression and protein synthesis by modulation of nuclear shape. Proc Natl Acad Sci U S A 99: 1972–1977, 2002.
 181. Thoumine O, Ott A. Time scale dependent viscoelastic and contractile regimes in fibroblasts probed by microplate manipulation. J Cell Sci 110 (Pt 17): 2109–2116, 1997.
 182. Towbin BD, Meister P, Gasser SM. The nuclear envelope—a scaffold for silencing? Curr Opin Genet Dev 19: 180–186, 2009.
 183. Tseng Y, Lee JS, Kole TP, Jiang I, Wirtz D. Micro‐organization and visco‐elasticity of the interphase nucleus revealed by particle nanotracking. J Cell Sci 117: 2159–2167, 2004.
 184. Vantyghem MC, Pigny P, Maurage CA, Rouaix‐Emery N, Stojkovic T, Cuisset JM, Millaire A, Lascols O, Vermersch P, Wemeau JL, Capeau J, Vigouroux C. Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities. J Clin Endocrinol Metab 89: 5337–5346, 2004.
 185. Varela I, Cadinanos J, Pendas AM, Gutierrez‐Fernandez A, Folgueras AR, Sanchez LM, Zhou Z, Rodriguez FJ, Stewart CL, Vega JA, Tryggvason K, Freije JM, Lopez‐Otin C. Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437: 564–568, 2005.
 186. Vaziri A, Mofrad MR. Mechanics and deformation of the nucleus in micropipette aspiration experiment. J Biomech 40: 2053–2062, 2007.
 187. Venables RS, McLean S, Luny D, Moteleb E, Morley S, Quinlan RA, Lane EB, Hutchison CJ. Expression of individual lamins in basal cell carcinomas of the skin. Br J Cancer 84: 512–519, 2001.
 188. Vergnes L, Peterfy M, Bergo MO, Young SG, Reue K. Lamin B1 is required for mouse development and nuclear integrity. Proc Natl Acad Sci U S A 101: 10428–10433, 2004.
 189. Verstraeten VL, Lammerding J. Experimental techniques for study of chromatin mechanics in intact nuclei and living cells. Chromosome Res 16: 499–510, 2008.
 190. Vigouroux C, Auclair M, Dubosclard E, Pouchelet M, Capeau J, Courvalin JC, Buendia B. Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene. J Cell Sci 114: 4459–4468, 2001.
 191. Warren DT, Zhang Q, Weissberg PL, Shanahan CM. Nesprins: Intracellular scaffolds that maintain cell architecture and coordinate cell function? Expert Rev Mol Med 7: 1–15, 2005.
 192. Wiche G. Role of plectin in cytoskeleton organization and dynamics. J Cell Sci 111 (Pt 17): 2477–2486, 1998.
 193. Wiesel N, Mattout A, Melcer S, Melamed‐Book N, Herrmann H, Medalia O, Aebi U, Gruenbaum Y. Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins. Proc Natl Acad Sci U S A 105: 180–185, 2008.
 194. Wilhelmsen K, Litjens SH, Kuikman I, Tshimbalanga N, Janssen H, Van Den Bout I, Raymond K, Sonnenberg A. Nesprin‐3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J Cell Biol 171: 799–810, 2005.
 195. Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE. Emerin interacts in vitro with the splicing‐associated factor, YT521‐B. Eur J Biochem 270: 2459–2466, 2003.
 196. Willis ND, Cox TR, Rahman‐Casans SF, Smits K, Przyborski SA, Van Den Brandt P, van Engeland M, Weijenberg M, Wilson RG, de Bruine A, Hutchison CJ. Lamin A/C is a risk biomarker in colorectal cancer. PLoS ONE 3: e2988, 2008.
 197. Wilson KL, Holaska JM, de Oca RM, Tifft K, Zastrow M, Segura‐Totten M, Mansharamani M, Bengtsson L. Nuclear membrane protein emerin: Roles in gene regulation, actin dynamics and human disease. Novartis Found Symp 264: 51–58; discussion 58–62, 227–230, 2005.
 198. Wolf K, Friedl P. Molecular mechanisms of cancer cell invasion and plasticity. Br J Dermatol 154: 11–15, 2006.
 199. Wolf K, Wu YI, Liu Y, Geiger J, Tam E, Overall C, Stack MS, Friedl P. Multi‐step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9: 893–904, 2007.
 200. Worman HJ, Fong LG, Muchir A, Young SG. Laminopathies and the long strange trip from basic cell biology to therapy. J Clin Invest 119: 1825–1836, 2009.
 201. Worman HJ, Gundersen GG. Here come the SUNs: A nucleocytoskeletal missing link. Trends Cell Biol 16: 67–69, 2006.
 202. Xiong H, Rivero F, Euteneuer U, Mondal S, Mana‐Capelli S, Larochelle D, Vogel A, Gassen B, Noegel AA. Dictyostelium Sun‐1 connects the centrosome to chromatin and ensures genome stability. Traffic 9: 708–724, 2008.
 203. Yabuki M, Miyake T, Doi Y, Fujiwara T, Hamazaki K, Yoshioka T, Horton AA, Utsumi K. Role of nuclear lamins in nuclear segmentation of human neutrophils. Physiol Chem Phys Med NMR 31: 77–84, 1999.
 204. Young KG, Kothary R. Spectrin repeat proteins in the nucleus. Bioessays 27: 144–152, 2005.
 205. Zastrow MS, Flaherty DB, Benian GM, Wilson KL. Nuclear titin interacts with A‐ and B‐type lamins in vitro and in vivo. J Cell Sci 119: 239–249, 2006.
 206. Zastrow MS, Vlcek S, Wilson KL. Proteins that bind A‐type lamins: Integrating isolated clues. J Cell Sci 117: 979–987, 2004.
 207. Zhang J, Felder A, Liu Y, Guo LT, Lange S, Dalton ND, Gu Y, Peterson KL, Mizisin AP, Shelton GD, Lieber RL, Chen J. Nesprin 1 is critical for nuclear positioning and anchorage. Hum Mol Genet 19: 329–341, 2010.
 208. Zhang Q, Bethmann C, Worth NF, Davies JD, Wasner C, Feuer A, Ragnauth CD, Yi Q, Mellad JA, Warren DT, Wheeler MA, Ellis JA, Skepper JN, Vorgerd M, Schlotter‐Weigel B, Weissberg PL, Roberts RG, Wehnert M, Shanahan CM. Nesprin‐1 and ‐2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet 16: 2816–2833, 2007.
 209. Zhang Q, Ragnauth CD, Skepper JN, Worth NF, Warren DT, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM. Nesprin‐2 is a multi‐isomeric protein that binds lamin and emerin at the nuclear envelope and forms a subcellular network in skeletal muscle. J Cell Sci 118: 673–687, 2005.
 210. Zhang Q, Skepper JN, Yang F, Davies JD, Hegyi L, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM. Nesprins: A novel family of spectrin‐repeat‐containing proteins that localize to the nuclear membrane in multiple tissues. J Cell Sci 114: 4485–4498, 2001.
 211. Zhang X, Lei K, Yuan X, Wu X, Zhuang Y, Xu T, Xu R, Han M. SUN1/2 and Syne/Nesprin‐1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice. Neuron 64: 173–187, 2009.
 212. Zhen YY, Libotte T, Munck M, Noegel AA, Korenbaum E. NUANCE, a giant protein connecting the nucleus and actin cytoskeleton. J Cell Sci 115: 3207–3222, 2002.
 213. Zink D, Fischer AH, Nickerson JA. Nuclear structure in cancer cells. Nat Rev Cancer 4: 677–687, 2004.

Related Articles:

Mechanotransduction
Stress Transmission within the Cell

Contact Editor

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

* Required Field

How to Cite

Jan Lammerding. Mechanics of the Nucleus. Compr Physiol 2011, 1: 783-807. doi: 10.1002/cphy.c100038