Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus

Abstract

Research in cellular mechanotransduction often focuses on how extracellular physical forces are converted into chemical signals at the cell surface. However, mechanical forces that are exerted on surface-adhesion receptors, such as integrins and cadherins, are also channelled along cytoskeletal filaments and concentrated at distant sites in the cytoplasm and nucleus. Here, we explore the molecular mechanisms by which forces might act at a distance to induce mechanochemical conversion in the nucleus and alter gene activities.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Structural connectivity and long-distance force propagation.
Figure 2: Mechanotransduction at a distance.
Figure 3: Molecular connectivity from the ECM to the nucleus.
Figure 4: Possible nuclear mechanochemical conversion mechanisms.

Similar content being viewed by others

References

  1. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nature Rev. Mol. Cell Biol. 7, 265–275 (2006).

    CAS  Google Scholar 

  2. Orr, A. W., Helmke, B. P., Blackman, B. R. & Schwartz, M. A. Mechanisms of mechanotransduction. Dev. Cell 10, 11–20 (2006).

    CAS  PubMed  Google Scholar 

  3. Chien, S. Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am. J. Physiol. Heart Circ. Physiol. 292, H1209–H1224 (2007).

    CAS  PubMed  Google Scholar 

  4. Tzima, E. et al. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437, 426–431 (2005).

    CAS  PubMed  Google Scholar 

  5. Hayakawa, K., Tatsumi, H. & Sokabe, M. Actin stress fibers transmit and focus force to activate mechanosensitive channels. J. Cell Sci. 121, 496–503 (2008).

    CAS  PubMed  Google Scholar 

  6. Matthews, B. D., Overby, D. R., Mannix, R. & Ingber, D. E. Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J. Cell Sci. 119, 508–518 (2006).

    CAS  PubMed  Google Scholar 

  7. Meyer, C. J. et al. Mechanical control of cyclic AMP signalling and gene transcription through integrins. Nature Cell Biol. 2, 666–668 (2000).

    CAS  PubMed  Google Scholar 

  8. Lele, T. P. et al. Mechanical forces alter zyxin unbinding kinetics within focal adhesions of living cells. J. Cell Physiol. 207, 187–194 (2006).

    CAS  PubMed  Google Scholar 

  9. Chicurel, M. E., Singer, R. H., Meyer, C. J. & Ingber, D. E. Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions. Nature 392, 730–733 (1998).

    CAS  PubMed  Google Scholar 

  10. Giannone, G. & Sheetz, M. P. Substrate rigidity and force define form through tyrosine phosphatase and kinase pathways. Trends Cell Biol. 16, 213–223 (2006).

    CAS  PubMed  Google Scholar 

  11. Dong, C., Skalak, R. & Sung, K. L. Cytoplasmic rheology of passive neutrophils. Biorheology 28, 557–567 (1991).

    CAS  PubMed  Google Scholar 

  12. Fung, Y. C. & Liu, S. Q. Elementary mechanics of the endothelium of blood vessels. J. Biomech. Eng. 115, 1–12 (1993).

    CAS  PubMed  Google Scholar 

  13. Heidemann, S. R., Kaech, S., Buxbaum, R. E. & Matus, A. Direct observations of the mechanical behaviors of the cytoskeleton in living fibroblasts. J. Cell Biol. 145, 109–122 (1999).

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Ingber, D. E. Tensegrity I. Cell structure and hierarchical systems biology. J. Cell Sci. 116, 1157–1173 (2003).

    CAS  PubMed  Google Scholar 

  15. Kumar, S. et al. Viscoelastic retraction of single living stress fibers and its impact on cell shape, cytoskeletal organization, and extracellular matrix mechanics. Biophys. J. 90, 3762–3773 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Brangwynne, C. P. et al. Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement. J. Cell Biol. 173, 733–741 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Vikstrom, K. L., Lim, S. S., Goldman, R. D. & Borisy, G. G. Steady state dynamics of intermediate filament networks. J. Cell Biol. 118, 121–129 (1992).

    CAS  PubMed  Google Scholar 

  18. Wang, N. & Suo, Z. Long-distance propagation of forces in a cell. Biochem. Biophys. Res. Commun. 328, 1133–1138 (2005).

    CAS  PubMed  Google Scholar 

  19. Ingber, D. E. Cellular mechanotransduction: putting all the pieces together again. FASEB J. 20, 811–827 (2006).

    CAS  PubMed  Google Scholar 

  20. Chowdhury, F. et al. Is cell rheology governed by nonequilibrium to equilibrium transition of noncovalent bonds? Biophys. J. 3 Oct 2008 (doi: 10.1529/biophysj.108.139832).

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Fey, E. G., Wan, K. M. & Penman, S. Epithelial cytoskeletal framework and nuclear matrix–intermediate filament scaffold: three-dimensional organization and protein composition. J. Cell Biol. 98, 1973–1984 (1984).

    CAS  PubMed  Google Scholar 

  22. Maniotis, A. J., Chen, C. S. & Ingber, D. E. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc. Natl Acad. Sci. USA 94, 849–854 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Ingber, D. E. The riddle of morphogenesis: a question of solution chemistry or molecular cell engineering? Cell 75, 1249–1252 (1993).

    CAS  PubMed  Google Scholar 

  24. Wang, N. et al. Mechanical behavior in living cells consistent with the tensegrity model. Proc. Natl Acad. Sci. USA 98, 7765–7770 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Knight, M. M. et al. Chondrocyte deformation induces mitochondrial distortion and heterogeneous intracellular strain fields. Biomech. Model. Mechanobiol. 5, 180–191 (2006).

    CAS  PubMed  Google Scholar 

  26. Silberberg, Y. R. et al. Mitochondrial displacements in response to nanomechanical forces. J. Mol. Recognit. 21, 30–36 (2008).

    CAS  PubMed  Google Scholar 

  27. Helmke, B. P., Rosen, A. B. & Davies, P. F. Mapping mechanical strain of an endogenous cytoskeletal network in living endothelial cells. Biophys. J. 84, 2691–2699 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Sims, J. R., Karp, S. & Ingber, D. E. Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape. J. Cell Sci. 103, 1215–1222 (1992).

    PubMed  Google Scholar 

  29. Hu, S., Chen, J., Butler, J. P. & Wang, N. Prestress mediates force propagation into the nucleus. Biochem. Biophys. Res. Commun. 329, 423–428 (2005).

    CAS  PubMed  Google Scholar 

  30. Hu, S. et al. Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells. Am. J. Physiol., Cell Physiol. 285, C1082–C1090 (2003).

    CAS  Google Scholar 

  31. Hu, S. et al. Mechanical anisotropy of adherent cells probed by a three-dimensional magnetic twisting device. Am. J. Physiol., Cell Physiol. 287, C1184–C1191 (2004).

    CAS  Google Scholar 

  32. Na, S. et al. Rapid signal transduction in living cells is a unique feature of mechanotransduction. Proc. Natl Acad. Sci. USA 105, 6626–6631 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Maniotis, A. J., Bojanowski, K. & Ingber, D. E. Mechanical continuity and reversible chromosome disassembly within intact genomes removed from living cells. J. Cell. Biochem. 65, 114–130 (1997).

    CAS  PubMed  Google Scholar 

  34. Zaidel-Bar, R., Itzkovitz, S., Ma'ayan, A., Iyengar, R. & Geiger, B. Functional atlas of the integrin adhesome. Nature Cell Biol. 9, 858–867 (2007).

    CAS  PubMed  Google Scholar 

  35. Homan, S. M., Martinez, R., Benware, A. & LaFlamme, S. E. Regulation of the association of α6β4 with vimentin intermediate filaments in endothelial cells. Exp. Cell Res. 281, 107–114 (2002).

    CAS  PubMed  Google Scholar 

  36. Gumbiner, B. M. Regulation of cadherin-mediated adhesion in morphogenesis. Nature Rev. Mol. Cell Biol. 6, 622–634 (2005).

    CAS  Google Scholar 

  37. Georgatos, S. D. & Blobel, G. Lamin B constitutes an intermediate filament attachment site at the nuclear envelope. J. Cell Biol. 105, 117–125 (1987).

    CAS  PubMed  Google Scholar 

  38. Georgatos, S. D. & Blobel, G. Two distinct attachment sites for vimentin along the plasma membrane and the nuclear envelope in avian erythrocytes: a basis for a vectorial assembly of intermediate filaments. J. Cell Biol. 105, 105–115 (1987).

    CAS  PubMed  Google Scholar 

  39. Crisp, M. et al. Coupling of the nucleus and cytoplasm: role of the LINC complex. J. Cell Biol. 172, 41–53 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Haque, F. et al. 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).

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Padmakumar, V. C. et al. The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope. J. Cell Sci. 118, 3419–3430 (2005).

    CAS  PubMed  Google Scholar 

  42. Worman, H. J. & Gundersen, G. G. Here come the SUNs: a nucleocytoskeletal missing link. Trends Cell Biol. 16, 67–69 (2006).

    CAS  PubMed  Google Scholar 

  43. Hodzic, D. M., Yeater, D. B., Bengtsson, L., Otto, H. & Stahl, P. D. Sun2 is a novel mammalian inner nuclear membrane protein. J. Biol. Chem. 279, 25805–25812 (2004).

    CAS  PubMed  Google Scholar 

  44. Zhang, X. et al. Syne-1 and Syne-2 play crucial roles in myonuclear anchorage and motor neuron innervation. Development 134, 901–908 (2007).

    CAS  PubMed  Google Scholar 

  45. Hansen, L. K. & Ingber, D. E. in Nuclear Trafficking (ed. Feldherr, C. M.) 71–86 (Academic Press, San Diego, 1992).

    Google Scholar 

  46. Liu, Q. et al. Functional association of Sun1 with nuclear pore complexes. J. Cell Biol. 178, 785–798 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Ketema, M. et al. Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin. J. Cell Sci. 120, 3384–3394 (2007).

    CAS  PubMed  Google Scholar 

  48. Wilhelmsen, K. et al. Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J. Cell Biol. 171, 799–810 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Starr, D. A. Communication between the cytoskeleton and the nuclear envelope to position the nucleus. Mol. Biosyst. 3, 583–589 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Malone, C. J. et al. The C. elegans hook protein, ZYG-12, mediates the essential attachment between the centrosome and nucleus. Cell 115, 825–836 (2003).

    CAS  PubMed  Google Scholar 

  51. McGee, M. D., Rillo, R., Anderson, A. S. & Starr, D. A. UNC-83 is a KASH protein required for nuclear migration and is recruited to the outer nuclear membrane by a physical interaction with the SUN protein UNC-84. Mol. Biol. Cell 17, 1790–1801 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Starr, D. A. et al. unc-83 encodes a novel component of the nuclear envelope and is essential for proper nuclear migration. Development 128, 5039–5050 (2001).

    CAS  PubMed  Google Scholar 

  53. Dechat, T. et al. Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev. 22, 832–853 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Lammerding, J. et al. Lamins A and C but not lamin B1 regulate nuclear mechanics. J. Biol. Chem. 281, 25768–25780 (2006).

    CAS  PubMed  Google Scholar 

  55. Lammerding, J. et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest. 113, 370–378 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Lee, K. K. et al. Distinct functional domains in emerin bind lamin A and DNA-bridging protein BAF. J. Cell Sci. 114, 4567–4573 (2001).

    CAS  PubMed  Google Scholar 

  57. Sakaki, M. et al. Interaction between emerin and nuclear lamins. J. Biochem. 129, 321–327 (2001).

    CAS  PubMed  Google Scholar 

  58. Worman, H. J., Yuan, J., Blobel, G. & Georgatos, S. D. A lamin B receptor in the nuclear envelope. Proc. Natl Acad. Sci. USA 85, 8531–8534 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Mislow, J. M. et al. Nesprin-1α self-associates and binds directly to emerin and lamin A in vitro. FEBS Lett. 525, 135–140 (2002).

    CAS  PubMed  Google Scholar 

  60. Wheeler, M. A. et al. Distinct functional domains in nesprin-1α and nesprin-2β bind directly to emerin and both interactions are disrupted in X-linked Emery–Dreifuss muscular dystrophy. Exp. Cell Res. 313, 2845–2857 (2007).

    CAS  PubMed  Google Scholar 

  61. Holaska, J. M. & Wilson, K. L. 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).

    CAS  PubMed  Google Scholar 

  62. Salpingidou, G., Smertenko, A., Hausmanowa-Petrucewicz, I., Hussey, P. J. & Hutchison, C. J. 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).

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Wilkinson, F. L. et al. Emerin interacts in vitro with the splicing-associated factor, YT521-B. Eur. J. Biochem. 270, 2459–2466 (2003).

    CAS  PubMed  Google Scholar 

  64. Holmer, L. & Worman, H. J. Inner nuclear membrane proteins: functions and targeting. Cell. Mol. Life Sci. 58, 1741–1747 (2001).

    CAS  PubMed  Google Scholar 

  65. Stewart-Hutchinson, P. J., Hale, C. M., Wirtz, D. & Hodzic, D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp. Cell Res. 314, 1892–1905 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Bloom, S., Lockard, V. G. & Bloom, M. Intermediate filament-mediated stretch-induced changes in chromatin: a hypothesis for growth initiation in cardiac myocytes. J. Mol. Cell. Cardiol. 28, 2123–2127 (1996).

    CAS  PubMed  Google Scholar 

  67. Pekny, M. & Lane, E. B. Intermediate filaments and stress. Exp. Cell Res. 313, 2244–2254 (2007).

    CAS  PubMed  Google Scholar 

  68. Mattout, A., Dechat, T., Adam, S. A., Goldman, R. D. & Gruenbaum, Y. Nuclear lamins, diseases and aging. Curr. Opin. Cell Biol. 18, 335–341 (2006).

    CAS  PubMed  Google Scholar 

  69. Barboro, P. et al. Unraveling the organization of the internal nuclear matrix: RNA-dependent anchoring of NuMA to a lamin scaffold. Exp. Cell Res. 279, 202–218 (2002).

    CAS  PubMed  Google Scholar 

  70. Hozak, P., Sasseville, A. M., Raymond, Y. & Cook, P. R. Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells. J. Cell Sci. 108, 635–644 (1995).

    CAS  PubMed  Google Scholar 

  71. Malyavantham, K. S. et al. Identifying functional neighborhoods within the cell nucleus: proximity analysis of early S-phase replicating chromatin domains to sites of transcription, RNA polymerase II, HP1γ, matrin 3 and SAF-A. J. Cell. Biochem. 105, 391–403 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Zastrow, M. S., Flaherty, D. B., Benian, G. M. & Wilson, K. L. Nuclear titin interacts with A- and B-type lamins in vitro and in vivo. J. Cell Sci. 119, 239–249 (2006).

    CAS  PubMed  Google Scholar 

  73. Granzier, H. L. & Labeit, S. The giant protein titin: a major player in myocardial mechanics, signaling, and disease. Circ. Res. 94, 284–295 (2004).

    CAS  PubMed  Google Scholar 

  74. Pederson, T. As functional nuclear actin comes into view, is it globular, filamentous, or both? J. Cell Biol. 180, 1061–1064 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Vreugde, S. et al. Nuclear myosin VI enhances RNA polymerase II-dependent transcription. Mol. Cell 23, 749–755 (2006).

    CAS  PubMed  Google Scholar 

  76. Ye, J., Zhao, J., Hoffmann-Rohrer, U. & Grummt, I. Nuclear myosin I acts in concert with polymeric actin to drive RNA polymerase I transcription. Genes Dev. 22, 322–330 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Holaska, J. M., Kowalski, A. K. & Wilson, K. L. Emerin caps the pointed end of actin filaments: evidence for an actin cortical network at the nuclear inner membrane. PLoS Biol. 2, e231 (2004).

    PubMed Central  PubMed  Google Scholar 

  78. Lattanzi, G. et al. Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts. Biochem. Biophys. Res. Commun. 303, 764–770 (2003).

    CAS  PubMed  Google Scholar 

  79. Bode, J., Goetze, S., Heng, H., Krawetz, S. A. & Benham, C. From DNA structure to gene expression: mediators of nuclear compartmentalization and dynamics. Chromosome Res. 11, 435–445 (2003).

    CAS  PubMed  Google Scholar 

  80. Chakalova, L., Debrand, E., Mitchell, J. A., Osborne, C. S. & Fraser, P. Replication and transcription: shaping the landscape of the genome. Nature Rev. Genet. 6, 669–677 (2005).

    CAS  PubMed  Google Scholar 

  81. Cook, P. R. Predicting three-dimensional genome structure from transcriptional activity. Nature Genet. 32, 347–352 (2002).

    CAS  PubMed  Google Scholar 

  82. Nickerson, J. A., Blencowe, B. J. & Penman, S. The architectural organization of nuclear metabolism. Int. Rev. Cytol. 162A, 167–123 (1995).

    Google Scholar 

  83. Durst, K. L. & Hiebert, S. W. Role of RUNX family members in transcriptional repression and gene silencing. Oncogene 23, 4220–4224 (2004).

    CAS  PubMed  Google Scholar 

  84. Stein, G. S. et al. Organization of transcriptional regulatory machinery in nuclear microenvironments: implications for biological control and cancer. Adv. Enzyme Regul. 47, 242–250 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Zaidi, S. K. et al. The dynamic organization of gene-regulatory machinery in nuclear microenvironments. EMBO Rep. 6, 128–133 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Stamenovic, D. & Ingber, D. E. Tensegrity-guided self assembly: from molecules to living cells. Soft Matter (in the press).

  87. Itano, N., Okamoto, S., Zhang, D., Lipton, S. A. & Ruoslahti, E. Cell spreading controls endoplasmic and nuclear calcium: a physical gene regulation pathway from the cell surface to the nucleus. Proc. Natl Acad. Sci. USA 100, 5181–5186 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Prat, A. G. & Cantiello, H. F. Nuclear ion channel activity is regulated by actin filaments. Am. J. Physiol. 270, C1532–C1543 (1996).

    CAS  PubMed  Google Scholar 

  89. Haraguchi, T. et al. 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).

    CAS  PubMed  Google Scholar 

  90. 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).

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Bentley, D. L. Rules of engagement: co-transcriptional recruitment of pre-mRNA processing factors. Curr. Opin. Cell Biol. 17, 251–256 (2005).

    CAS  PubMed  Google Scholar 

  92. Blencowe, B. J., Nickerson, J. A., Issner, R., Penman, S. & Sharp, P. A. Association of nuclear matrix antigens with exon-containing splicing complexes. J. Cell Biol. 127, 593–607 (1994).

    CAS  PubMed  Google Scholar 

  93. Lange, S. et al. The kinase domain of titin controls muscle gene expression and protein turnover. Science 308, 1599–1603 (2005).

    CAS  PubMed  Google Scholar 

  94. Feldherr, C. M. & Akin, D. The permeability of the nuclear envelope in dividing and nondividing cell cultures. J. Cell Biol. 111, 1–8 (1990).

    CAS  PubMed  Google Scholar 

  95. Kohler, A., Schneider, M., Cabal, G. G., Nehrbass, U. & Hurt, E. Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export. Nature Cell Biol. 10, 707–715 (2008).

    PubMed  Google Scholar 

  96. Yen, A. & Pardee, A. B. Role of nuclear size in cell growth initiation. Science 204, 1315–1317 (1979).

    CAS  PubMed  Google Scholar 

  97. Kouzine, F., Sanford, S., Elisha-Feil, Z. & Levens, D. The functional response of upstream DNA to dynamic supercoiling in vivo. Nature Struct. Mol. Biol. 15, 146–154 (2008).

    CAS  Google Scholar 

  98. Liu, J. et al. The FUSE/FBP/FIR/TFIIH system is a molecular machine programming a pulse of c-myc expression. EMBO J. 25, 2119–2130 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Luo, Y., Xu, X., Lele, T., Kumar, S. & Ingber, D. E. A multi-modular tensegrity model of an actin stress fiber. J. Biomech. 41, 2379–2387 (2008).

    PubMed Central  PubMed  Google Scholar 

  100. Janmey, P. A., Euteneuer, U., Traub, P. & Schliwa, M. Viscoelastic properties of vimentin compared with other filamentous biopolymer networks. J. Cell Biol. 113, 155–160 (1991).

    CAS  PubMed  Google Scholar 

  101. Pajerowski, J. D., Dahl, K. N., Zhong, F. L., Sammak, P. J. & Discher, D. E. Physical plasticity of the nucleus in stem cell differentiation. Proc. Natl Acad. Sci. USA 104, 15619–15624 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. de Lanerolle, P., Johnson, T. & Hofmann, W. A. Actin and myosin I in the nucleus: what next? Nature Struct. Mol. Biol. 12, 742–746 (2005).

    CAS  Google Scholar 

  103. Hahn, C. & Schwartz, M. A. Mechanotransduction in vascular physiology and atherogenesis. Nature Rev. Mol. Cell Biol. 23 Dec 2008 (doi: 10.1038/nrm2596).

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Chalfie, M. Neurosensory mechanotransduction. Nature Rev. Mol. Cell Biol. 23 Dec 2008 (doi: 10.1038/nrm2595).

    CAS  PubMed  Google Scholar 

  105. Jaalouk, D. E. & Lammerding, J. Mechanotransduction gone awry. Nature Rev. Mol. Cell Biol. 23 Dec 2008 (doi: 10.1038/nrm2597).

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Geiger, B., Spatz, J. P. & Bershadsky, A. D. Environmental sensing by cells through focal adhesions. Nature Rev. Mol. Cell Biol. 23 Dec 2008 (doi: 10.1038/nrm2593)

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank E. Xuan, A. Maniotis and S. Na for providing Fig. 1a, Fig. 1b,c and Fig. 2b, respectively, and A. Maniotis and J. Karavitis for permission to use their movie of chromosome pulling. This work was supported by grants from the National Institutes of Health (to N.W., J.T. and D.E.I.) and a Department of Defense Breast Cancer Innovator Award (to D.E.I.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Donald E. Ingber.

Supplementary information

Supplementary information S1 (movie)| Mechanical continuity in the genome

A movie showing mechanical continuity in the human genome within a living mitotic endothelial cell visualized by harpooning a single chromosome using a glass microneedle, as shown in FIG. 1c and REF. 1 (Kindly provided by A. Maniotis, U. of Illinois at Chicago). (MOV 7508 kb)

41580_2009_BFnrm2594_MOESM2_ESM.pdf

Related links

Related links

DATABASES

OMIM

Emery–Dreifuss muscular dystrophy

Interpro

KASH

FURTHER INFORMATION

Ning Wang's homepage

The Ingber Laboratory

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, N., Tytell, J. & Ingber, D. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10, 75–82 (2009). https://doi.org/10.1038/nrm2594

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2594

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing