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.

  • Review Article
  • Published:

Mechanotransduction gone awry

Key Points

  • Mechanotransduction describes the cellular processes that translate mechanical inputs into biochemical signals and can modulate cellular functions as diverse as migration, proliferation, differentiation and apoptosis.

  • Mechanotransduction is essential in the development and maintenance of all tissues, but is particularly important in mechanically-stressed tissues such as muscle, bone, cartilage and blood vessels, as these require adaptive responses to quickly adjust to varying loading conditions.

  • Changes in cellular or extracellular structure, the cellular mechanosensing process itself or in the relevant downstream signalling pathways can result in altered and abnormal mechanotransduction and can lead to disease.

  • Diseases associated with disturbed mechanotransduction signalling include developmental defects, loss of hearing, muscular dystrophies, cardiac myopathies, defects in bone and cartilage, axial myopia, glaucoma, arteriosclerosis and cancer.

  • A common denominator of many mechanobiology diseases is a disruption in the intricate force transmission between the extracellular matrix (ECM), the cytoskeleton and the nuclear interior.

  • Sudden changes in ECM mechanics, ECM remodelling and the resultant disturbance in cytoskeletal tension and mechanotransduction signalling have emerged as important factors that can promote malignant transformation, tumorigenesis and metastasis.

Abstract

Cells sense their physical surroundings through mechanotransduction — that is, by translating mechanical forces and deformations into biochemical signals such as changes in intracellular calcium concentration or by activating diverse signalling pathways. In turn, these signals can adjust cellular and extracellular structure. This mechanosensitive feedback modulates cellular functions as diverse as migration, proliferation, differentiation and apoptosis, and is crucial for organ development and homeostasis. Consequently, defects in mechanotransduction — often caused by mutations or misregulation of proteins that disturb cellular or extracellular mechanics — are implicated in the development of various diseases, ranging from muscular dystrophies and cardiomyopathies to cancer progression and metastasis.

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: Mechanotransduction in hair cells.
Figure 2: Force transmission between the extracellular matrix and the nucleus.
Figure 3: Unifying characteristics of mechanotransduction disorders.
Figure 4: Cardiac mechanotransduction signalling.
Figure 5: Mechanotransduction in cancer cells.

Similar content being viewed by others

References

  1. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    CAS  PubMed  Google Scholar 

  2. Paszek, M. J. et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 8, 241–254 (2005). Presents an elegant study linking matrix stiffness and cytoskeletal tension to cancer progression. As a component of a 'mechano-regulatory circuit' that includes integrins, Rho and ERK, disruption of tensional homeostasis can promote a malignant phenotype in a model of breast cancer.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  4. 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 

  5. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nature Rev. Mol. Cell Biol. 7, 265–275 (2006). This is a comprehensive review of the literature on how physical cues in the microenvironment of a eukaryotic cell are sensed and converted to biochemical signals that define cell shape and regulate cell growth, differentiation and survival.

    CAS  Google Scholar 

  6. Vollrath, M. A., Kwan, K. Y. & Corey, D. P. The micromachinery of mechanotransduction in hair cells. Annu. Rev. Neurosci. 30, 339–365 (2007). Provides a detailed and mechanistic review of the process of mechanotransduction in hearing. It describes the constituents of this process from the mechanosensory elements in the inner ear to the genetic determinants (mutations that are attributed to hearing loss).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Eberl, D. F., Hardy, R. W. & Kernan, M. J. Genetically similar transduction mechanisms for touch and hearing in Drosophila. J. Neurosci. 20, 5981–5988 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Syntichaki, P. & Tavernarakis, N. Genetic models of mechanotransduction: the nematode Caenorhabditis elegans. Physiol. Rev. 84, 1097–1153 (2004).

    CAS  PubMed  Google Scholar 

  9. Lammerding, J., Kamm, R. D. & Lee, R. T. Mechanotransduction in cardiac myocytes. Ann. NY Acad. Sci. 1015, 53–70 (2004). An overview of the signalling pathways that are implicated in cardiomyocyte mechanotransduction that discusses the diverse responses of a cardiac myocyte in its adaptation to alterations in its mechanical environment.

    PubMed  Google Scholar 

  10. Garcia-Cardena, G., Comander, J., Anderson, K. R., Blackman, B. R. & Gimbrone, M. A. Jr. Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proc. Natl Acad. Sci. USA 98, 4478–4485 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Gimbrone, M. A., Jr, Topper, J. N., Nagel, T., Anderson, K. R. & Garcia-Cardena, G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann. NY Acad. Sci. 902, 230–240 (2000).

    CAS  PubMed  Google Scholar 

  12. Haga, J. H., Li, Y. S. & Chien, S. Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells. J. Biomech. 40, 947–960 (2007).

    PubMed  Google Scholar 

  13. Li, Y. S., Haga, J. H. & Chien, S. Molecular basis of the effects of shear stress on vascular endothelial cells. J. Biomech. 38, 1949–1971 (2005).

    PubMed  Google Scholar 

  14. Ng, C. P., Helm, C. L. & Swartz, M. A. Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. Microvasc. Res. 68, 258–264 (2004).

    PubMed  Google Scholar 

  15. Hammerschmidt, S., Kuhn, H., Gessner, C., Seyfarth, H. J. & Wirtz, H. Stretch-induced alveolar type II cell apoptosis: role of endogenous bradykinin and PI3K-Akt signaling. Am. J. Respir. Cell Mol. Biol. 37, 699–705 (2007).

    CAS  PubMed  Google Scholar 

  16. Burger, E. H. & Klein-Nulend, J. Mechanotransduction in bone — role of the lacuno-canalicular network. FASEB J. 13, S101–S112 (1999).

    CAS  PubMed  Google Scholar 

  17. Wirtz, H. R. & Dobbs, L. G. The effects of mechanical forces on lung functions. Respir. Physiol. 119, 1–17 (2000).

    CAS  PubMed  Google Scholar 

  18. Serluca, F. C., Drummond, I. A. & Fishman, M. C. Endothelial signaling in kidney morphogenesis: a role for hemodynamic forces. Curr. Biol. 12, 492–497 (2002).

    CAS  PubMed  Google Scholar 

  19. Cheng, C. et al. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 113, 2744–2753 (2006).

    PubMed  Google Scholar 

  20. Klein-Nulend, J., Bacabac, R. G., Veldhuijzen, J. P. & Van Loon, J. J. Microgravity and bone cell mechanosensitivity. Adv. Space Res. 32, 1551–1559 (2003).

    CAS  PubMed  Google Scholar 

  21. Uhlig, S. Ventilation-induced lung injury and mechanotransduction: stretching it too far? Am. J. Physiol. Lung Cell Mol. Physiol. 282, L892–L896 (2002).

    CAS  PubMed  Google Scholar 

  22. Affonce, D. A. & Lutchen, K. R. New perspectives on the mechanical basis for airway hyperreactivity and airway hypersensitivity in asthma. J. Appl. Physiol. 101, 1710–1719 (2006).

    PubMed  Google Scholar 

  23. Ichimura, H., Parthasarathi, K., Quadri, S., Issekutz, A. C. & Bhattacharya, J. Mechano-oxidative coupling by mitochondria induces proinflammatory responses in lung venular capillaries. J. Clin. Invest. 111, 691–699 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Matheson, L. A., Maksym, G. N., Santerre, J. P. & Labow, R. S. Cyclic biaxial strain affects U937 macrophage-like morphology and enzymatic activities. J. Biomed. Mater. Res. A 76, 52–62 (2006).

    PubMed  Google Scholar 

  25. Coughlin, M. F., Sohn, D. D. & Schmid-Schonbein, G. W. Recoil and stiffening by adherent leukocytes in response to fluid shear. Biophys. J. 94, 1046–1051 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Ji, J. Y., Jing, H. & Diamond, S. L. Hemodynamic regulation of inflammation at the endothelial–neutrophil interface. Ann. Biomed. Eng. 36, 586–595 (2008).

    PubMed  Google Scholar 

  27. Ostrow, L. W. & Sachs, F. Mechanosensation and endothelin in astrocytes—hypothetical roles in CNS pathophysiology. Brain Res. Brain Res. Rev. 48, 488–508 (2005).

    CAS  PubMed  Google Scholar 

  28. Jacques-Fricke, B. T., Seow, Y., Gottlieb, P. A., Sachs, F. & Gomez, T. M. Ca2+ influx through mechanosensitive channels inhibits neurite outgrowth in opposition to other influx pathways and release from intracellular stores. J. Neurosci. 26, 5656–5664 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Lansman, J. B. & Franco-Obregon, A. Mechanosensitive ion channels in skeletal muscle: a link in the membrane pathology of muscular dystrophy. Clin. Exp. Pharmacol. Physiol. 33, 649–656 (2006).

    CAS  PubMed  Google Scholar 

  30. Holaska, J. M. Emerin and the nuclear lamina in muscle and cardiac disease. Circ. Res. 103, 16–23 (2008).

    CAS  PubMed  Google Scholar 

  31. Marian, A. J. Genetic determinants of cardiac hypertrophy. Curr. Opin. Cardiol. 23, 199–205 (2008).

    PubMed  PubMed Central  Google Scholar 

  32. Barry, S. P., Davidson, S. M. & Townsend, P. A. Molecular regulation of cardiac hypertrophy. Int. J. Biochem. Cell Biol. 40, 2023–2039 (2008).

    CAS  PubMed  Google Scholar 

  33. Heineke, J. & Molkentin, J. D. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nature Rev. Mol. Cell Biol. 7, 589–600 (2006).

    CAS  Google Scholar 

  34. Grossman, W., Jones, D. & McLaurin, L. P. Wall stress and patterns of hypertrophy in the human left ventricle. J. Clin. Invest. 56, 56–64 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Palmer, B. M. Thick filament proteins and performance in human heart failure. Heart Fail. Rev. 10, 187–197 (2005).

    CAS  PubMed  Google Scholar 

  36. Heydemann, A. & McNally, E. M. Consequences of disrupting the dystrophin–sarcoglycan complex in cardiac and skeletal myopathy. Trends Cardiovasc. Med. 17, 55–59 (2007). Provides a neat example of how abnormalities in structural proteins that are implicated in intracellular force transmission and in cell-matrix coupling can result in disease. It describes how mutations in the dystrophin–glycoprotein complex contribute to the aetiology of cardiac and skeletal myopathy.

    CAS  PubMed  Google Scholar 

  37. Kumar, A., Khandelwal, N., Malya, R., Reid, M. B. & Boriek, A. M. Loss of dystrophin causes aberrant mechanotransduction in skeletal muscle fibers. FASEB J. 18, 102–113 (2004).

    CAS  PubMed  Google Scholar 

  38. Claflin, D. R. & Brooks, S. V. Direct observation of failing fibers in muscles of dystrophic mice provides mechanistic insight into muscular dystrophy. Am. J. Physiol. Cell Physiol. 294, C651–C658 (2008).

    CAS  PubMed  Google Scholar 

  39. Loufrani, L. et al. Absence of dystrophin in mice reduces NO-dependent vascular function and vascular density: total recovery after a treatment with the aminoglycoside gentamicin. Arterioscler. Thromb. Vasc. Biol. 24, 671–676 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Hoshijima, M. Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures. Am. J. Physiol. Heart Circ. Physiol. 290, H1313–H1325 (2006).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Lammerding, J. et al. Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells. J. Cell Biol. 170, 781–791 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Tan, J. C., Kalapesi, F. B. & Coroneo, M. T. Mechanosensitivity and the eye: cells coping with the pressure. Br. J. Ophthalmol. 90, 383–388 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Johnstone, M. A. The aqueous outflow system as a mechanical pump: evidence from examination of tissue and aqueous movement in human and non-human primates. J. Glaucoma 13, 421–438 (2004).

    PubMed  Google Scholar 

  45. Cui, W., Bryant, M. R., Sweet, P. M. & McDonnell, P. J. Changes in gene expression in response to mechanical strain in human scleral fibroblasts. Exp. Eye Res. 78, 275–284 (2004).

    CAS  PubMed  Google Scholar 

  46. Hove, J. R. et al. Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421, 172–177 (2003).

    CAS  PubMed  Google Scholar 

  47. Lecuit, T. & Lenne, P. F. Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nature Rev. Mol. Cell Biol. 8, 633–644 (2007). In addition to providing a concise review of the role of cell-surface mechanics in embryonic and tissue morphogenesis, this paper poses questions that are of vital importance to our understanding of developmental phenomena.

    CAS  Google Scholar 

  48. Krieg, M. et al. Tensile forces govern germ-layer organization in zebrafish. Nature Cell Biol. 10, 429–436 (2008).

    CAS  PubMed  Google Scholar 

  49. Moore, K. A. et al. Control of basement membrane remodeling and epithelial branching morphogenesis in embryonic lung by Rho and cytoskeletal tension. Dev. Dyn. 232, 268–281 (2005).

    CAS  PubMed  Google Scholar 

  50. Patwari, P. & Lee, R. T. Mechanical control of tissue morphogenesis. Circ. Res. 103, 234–243 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Nauli, S. M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nature Genet. 33, 129–137 (2003).

    CAS  PubMed  Google Scholar 

  52. Delmas, P. Polycystins: from mechanosensation to gene regulation. Cell 118, 145–148 (2004). This review sums up the literature on polycystin proteins and their roles as mechanically gated channels in mediating mechanosensation in kidney cells as well as in regulating gene expression.

    CAS  PubMed  Google Scholar 

  53. Al-Shali, K. Z. & Hegele, R. A. Laminopathies and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 24, 1591–1595 (2004).

    CAS  PubMed  Google Scholar 

  54. Stehbens, W. E., Delahunt, B., Shozawa, T. & Gilbert-Barness, E. Smooth muscle cell depletion and collagen types in progeric arteries. Cardiovasc. Pathol. 10, 133–136 (2001).

    CAS  PubMed  Google Scholar 

  55. Capell, B. C., Collins, F. S. & Nabel, E. G. Mechanisms of cardiovascular disease in accelerated aging syndromes. Circ. Res. 101, 13–26 (2007).

    CAS  PubMed  Google Scholar 

  56. Davies, P. F. Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75, 519–560 (1995).

    CAS  PubMed  Google Scholar 

  57. Verstraeten, V. L., Ji, J. Y., Cummings, K. S., Lee, R. T. & Lammerding, J. Increased mechanosensitivity and nuclear stiffness in Hutchinson–Gilford progeria cells: effects of farnesyltransferase inhibitors. Aging Cell 7, 383–393 (2008).

    CAS  PubMed  Google Scholar 

  58. Huang, S. & Ingber, D. E. Cell tension, matrix mechanics, and cancer development. Cancer Cell 8, 175–176 (2005).

    CAS  PubMed  Google Scholar 

  59. Wolf, K. et al. Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nature Cell Biol. 9, 893–904 (2007).

    CAS  PubMed  Google Scholar 

  60. Suresh, S. Biomechanics and biophysics of cancer cells. Acta Biomater. 3, 413–438 (2007).

    PubMed  PubMed Central  Google Scholar 

  61. Clark, E. A., Golub, T. R., Lander, E. S. & Hynes, R. O. Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406, 532–535 (2000).

    CAS  PubMed  Google Scholar 

  62. Sahai, E. & Marshall, C. J. RHO-GTPases and cancer. Nature Rev. Cancer 2, 133–142 (2002).

    Google Scholar 

  63. Horiuchi, A. et al. Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. Lab. Invest. 83, 861–870 (2003).

    CAS  PubMed  Google Scholar 

  64. Lozano, E., Betson, M. & Braga, V. M. Tumor progression: Small GTPases and loss of cell–cell adhesion. Bioessays 25, 452–463 (2003).

    CAS  PubMed  Google Scholar 

  65. Sahai, E. & Marshall, C. J. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nature Cell Biol. 5, 711–719 (2003).

    CAS  PubMed  Google Scholar 

  66. Burridge, K. & Wennerberg, K. Rho and Rac take center stage. Cell 116, 167–179 (2004).

    CAS  PubMed  Google Scholar 

  67. Paszek, M. J. & Weaver, V. M. The tension mounts: mechanics meets morphogenesis and malignancy. J. Mammary Gland Biol. Neoplasia 9, 325–342 (2004).

    PubMed  Google Scholar 

  68. Sarntinoranont, M., Rooney, F. & Ferrari, M. Interstitial stress and fluid pressure within a growing tumor. Ann. Biomed. Eng. 31, 327–335 (2003).

    PubMed  Google Scholar 

  69. Hebner, C., Weaver, V. M. & Debnath, J. Modeling morphogenesis and oncogenesis in three-dimensional breast epithelial cultures. Annu. Rev. Pathol. 3, 313–339 (2008).

    CAS  PubMed  Google Scholar 

  70. Gaggioli, C. et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nature Cell Biol. 9, 1392–1400 (2007).

    CAS  PubMed  Google Scholar 

  71. Huang, S. & Ingber, D. E. The structural and mechanical complexity of cell-growth control. Nature Cell Biol. 1, E131–E138 (1999).

    CAS  PubMed  Google Scholar 

  72. Wang, H. B., Dembo, M. & Wang, Y. L. Substrate flexibility regulates growth and apoptosis of normal but not transformed cells. Am. J. Physiol. Cell Physiol. 279, C1345–C1350 (2000).

    CAS  PubMed  Google Scholar 

  73. Liang, S., Slattery, M. J., Wagner, D., Simon, S. I. & Dong, C. Hydrodynamic shear rate regulates melanoma-leukocyte aggregation, melanoma adhesion to the endothelium, and subsequent extravasation. Ann. Biomed. Eng. 36, 661–671 (2008).

    PubMed  PubMed Central  Google Scholar 

  74. Cross, S. E. et al. Nanomechanical properties of glucans and associated cell-surface adhesion of Streptococcus mutans probed by atomic force microscopy under in situ conditions. Microbiology 153, 3124–3132 (2007).

    CAS  PubMed  Google Scholar 

  75. Guck, J. et al. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88, 3689–3698 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Ochalek, T., Nordt, F. J., Tullberg, K. & Burger, M. M. Correlation between cell deformability and metastatic potential in B16-F1 melanoma cell variants. Cancer Res. 48, 5124–5128 (1988).

    CAS  PubMed  Google Scholar 

  77. Lee, S. E., Kamm, R. D. & Mofrad, M. R. Force-induced activation of talin and its possible role in focal adhesion mechanotransduction. J. Biomech. 40, 2096–2106 (2007).

    PubMed  Google Scholar 

  78. Mattout-Drubezki, A. & Gruenbaum, Y. Dynamic interactions of nuclear lamina proteins with chromatin and transcriptional machinery. Cell Mol. Life Sci. 60, 2053–2063 (2003).

    CAS  PubMed  Google Scholar 

  79. Fong, L. G. et al. Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J. Clin. Invest. 116, 743–752 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Yasuda, S. et al. Dystrophic heart failure blocked by membrane sealant poloxamer. Nature 436, 1025–1029 (2005).

    CAS  PubMed  Google Scholar 

  81. Ng, R., Metzger, J. M., Claflin, D. R. & Faulkner, J. A. Poloxamer 188 reduces the contraction-induced force decline in lumbrical muscles from Mdx mice. Am. J. Physiol. Cell Physiol. 295, C146–C150 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Perozo, E. Gating prokaryotic mechanosensitive channels. Nature Rev. Mol. Cell Biol. 7, 109–119 (2006).

    CAS  Google Scholar 

  83. Holt, J. R. & Corey, D. P. Two mechanisms for transducer adaptation in vertebrate hair cells. Proc. Natl Acad. Sci. USA 97, 11730–11735 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 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  PubMed Central  Google Scholar 

  85. Chang, A. N. & Potter, J. D. Sarcomeric protein mutations in dilated cardiomyopathy. Heart Fail. Rev. 10, 225–235 (2005).

    CAS  PubMed  Google Scholar 

  86. Nonaka, S. et al. Randomization of left–right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95, 829–837 (1998).

    CAS  PubMed  Google Scholar 

  87. Dong, C., Slattery, M. J., Liang, S. & Peng, H. H. Melanoma cell extravasation under flow conditions is modulated by leukocytes and endogenously produced interleukin 8. Mol. Cell Biomech. 2, 145–159 (2005).

    PubMed  PubMed Central  Google Scholar 

  88. Wozniak, M. A. & Chen, C. S. Mechanotransduction in development: a growing role for contractility. Nature Rev. Mol. Cell Biol. 23 Dec 2008 (doi: 10.1038/nrm2592).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  90. 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  PubMed Central  Google Scholar 

Download references

Acknowledgements

We apologize to all those authors whose papers we could not cite because of space limitations. We thank R. T. Lee and P. Patwari for insightful discussions and helpful comments. This work was supported by National Institutes of Health grants HL082792, NS059348, the American Heart Association grant 0635359N and a research grant from the Progeria Research Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jan Lammerding.

Related links

Related links

DATABASES

OMIM

Duchenne muscular dystrophy

Emery–Dreifuss muscular dystrophy

Hutchinson–Gilford progeria syndrome

Kartagener's syndrome

FURTHER INFORMATION

Jan Lammerding's homepage

Glossary

Sensory cells

Cells involved in the sensory reception of touch or hearing, often using specialized cellular structures such as hair bundles or proteins (for example, stretch-activated ion channels) to detect applied forces and deformations.

Vascular smooth muscle cells

Non-striated muscle cells found in the medial layer of arteries and arterioles. These cells are involved in regulating blood pressure and vessel tone.

Mechanosensitive proteins

Proteins that are directly involved in sensing forces or deformations. Microscopic forces result in conformational changes in these proteins, thereby altering their affinity to binding partners or ion conductivity and initiating downstream signalling pathways.

Stereocilia

Finger-like cytoplasmic extensions that project from the apical end of the inner ear's hair cells into the cochlear fluid. Stereocilia respond to fluid movement and changes in fluid pressure to mediate various sensory functions, including hearing.

Motor proteins

Proteins that generate the intracellular forces that are required for molecular transport or cell tension and contractility. Include dynein and kinesin.

Cilia

Hair-like projections on the outer surface of some cell types and unicellular organisms. Beating in unison in wave-like motion, cilia serve multiple functions including mechanosensing, motility and feeding.

Deafness genes

A set of genes, including the cadherin-23 gene, that encode tip link proteins, which are found in the hair cells in the inner ear and play a central role in the conversion of physical stimuli into electrochemical signals. Mutations in these genes can cause deafness.

Stretch-sensitive ion channels

Ion channels that can change their conformation from closed to open in response to mechanical strain in the membrane.

Sarcomeres

Basic functional units in striated muscle cells, consisting mostly of thick myosin filaments and thin actin filaments to generate forces.

Aortic stenosis

A condition that is characterized by abnormal narrowing of the valve opening between the left ventricle and the aorta in the heart, restricting blood flow and impeding the ability of the heart to pump blood to the body.

Ventricular wall stress

The mechanical stress, that is force per unit area, in the myocardium. Decrease in wall thickness, following loss of myocytes after infarction can result in increased left ventricular stress and can damage the remaining myocytes.

Interstitial fibrosis

A progressive condition that is characterized by fibrous connective tissue replacing normal tissue, such as muscle, that is lost by injury or by infection and infiltration of inflammatory cells into the small spaces between tissues.

Haemodynamic load

The forces that are generated from cardiac output and physical resistances due to the flow of blood in circulation.

Glaucoma

A disease in which the optic nerve is permanently damaged due to abnormally high fluid pressure in the eye. Results in impaired or complete loss of vision.

Axial myopia

Near- or short-sightedness associated with an increase in the eye's axial length.

Intraocular pressure

The pressure inside the eyeball that is generated by resistance to the outward fluid flow of aqueous humour. This pressure helps maintain the shape of the eye, but can result in glaucoma if it is too high.

Focal adhesions

Dynamic protein complexes at the plasma membrane that connect the extracellular matrix to the actin cytoskeleton. Focal adhesions consist of integrins, talin, paxillin and signalling molecules such as focal adhesion kinase. Several of these proteins are thought to act as mechanosensors and to participate in mechanotransduction signalling.

Pleural effusions

Fluids that collect in the space between the lungs and the chest wall.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jaalouk, D., Lammerding, J. Mechanotransduction gone awry. Nat Rev Mol Cell Biol 10, 63–73 (2009). https://doi.org/10.1038/nrm2597

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2597

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