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:

Cell mechanics and the cytoskeleton

Abstract

The ability of a eukaryotic cell to resist deformation, to transport intracellular cargo and to change shape during movement depends on the cytoskeleton, an interconnected network of filamentous polymers and regulatory proteins. Recent work has demonstrated that both internal and external physical forces can act through the cytoskeleton to affect local mechanical properties and cellular behaviour. Attention is now focused on how cytoskeletal networks generate, transmit and respond to mechanical signals over both short and long timescales. An important insight emerging from this work is that long-lived cytoskeletal structures may act as epigenetic determinants of cell shape, function and fate.

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: Elements of the cytoskeleton.
Figure 2: Building cytoskeletal structures.
Figure 3: Form meets function.
Figure 4: Force and shape.
Figure 5: Learning by building.

Similar content being viewed by others

References

  1. Weiss, P. A. in The Molecular Control of Cellular Activity (ed. Allen, J. M.) 1–72 (McGraw-Hill, 1961).

    Google Scholar 

  2. dos Remedios, C. G. et al. Actin binding proteins: regulation of cytoskeletal microfilaments. Physiol. Rev. 83, 433–473 (2003).

    Article  PubMed  CAS  Google Scholar 

  3. Machesky, L. M. et al. Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex. Proc. Natl Acad. Sci. USA 96, 3739–3744 (1999).

    Article  ADS  PubMed  CAS  Google Scholar 

  4. Weiner, O. D., Marganski, W. A., Wu, L. F., Altschuler, S. J. & Kirschner, M. W. An actin-based wave generator organizes cell motility. PLoS Biol. 5, e221 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Bieling, P. et al. Reconstitution of a microtubule plus-end tracking system in vitro. Nature 450, 1100–1105 (2007).

    Article  ADS  PubMed  CAS  Google Scholar 

  6. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Jordan, M. A. & Wilson, L. Microtubules as a target for anticancer drugs. Nature Rev. Cancer 4, 253–265 (2004).

    Article  CAS  Google Scholar 

  8. Mitchison, T. & Kirschner, M. Dynamic instability of microtubule growth. Nature 312, 237–242 (1984).

    Article  ADS  PubMed  CAS  Google Scholar 

  9. Holy, T. E. & Leibler, S. Dynamic instability of microtubules as an efficient way to search in space. Proc. Natl Acad. Sci. USA 91, 5682–5685 (1994). This paper showed that microtubule dynamics have a central role in spatial organization within cells.

    Article  ADS  PubMed  CAS  Google Scholar 

  10. Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003).

    Article  PubMed  CAS  Google Scholar 

  11. Parent, C. A. Making all the right moves: chemotaxis in neutrophils and Dictyostelium . Curr. Opin. Cell Biol. 16, 4–13 (2004).

    Article  PubMed  CAS  Google Scholar 

  12. Naumanen, P., Lappalainen, P. & Hotulainen, P. Mechanisms of actin stress fibre assembly. J. Microsc. 231, 446–454 (2008).

    Article  MathSciNet  PubMed  CAS  Google Scholar 

  13. Wiche, G. Role of plectin in cytoskeleton organization and dynamics. J. Cell Sci. 111, 2477–2486 (1998).

    PubMed  CAS  Google Scholar 

  14. Flitney, E. W., Kuczmarski, E. R., Adam, S. A. & Goldman, R. D. Insights into the mechanical properties of epithelial cells: the effects of shear stress on the assembly and remodeling of keratin intermediate filaments. FASEB J. 23, 2110–2119 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Tsai, M. Y. et al. A mitotic lamin B matrix induced by RanGTP required for spindle assembly. Science 311, 1887–1893 (2006).

    Article  ADS  PubMed  CAS  Google Scholar 

  16. Nedelec, F. J., Surrey, T., Maggs, A. C. & Leibler, S. Self-organization of microtubules and motors. Nature 389, 305–308 (1997).

    Article  ADS  PubMed  CAS  Google Scholar 

  17. Heald, R. et al. Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382, 420–425 (1996). The reconstitution of spindles in a cell extract, as reported in this paper, was a remarkable demonstration of the self-assembling properties of the cytoskeleton.

    Article  ADS  PubMed  CAS  Google Scholar 

  18. Mullins, R. D., Heuser, J. A. & Pollard, T. D. The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. Proc. Natl Acad. Sci. USA 95, 6181–6186 (1998). This paper presented the dendritic nucleation model for the assembly of branched actin networks.

    Article  ADS  PubMed  CAS  Google Scholar 

  19. Bailly, M. et al. Relationship between Arp2/3 complex and the barbed ends of actin filaments at the leading edge of carcinoma cells after epidermal growth factor stimulation. J. Cell Biol. 145, 331–345 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Svitkina, T. M. & Borisy, G. G. Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J. Cell Biol. 145, 1009–1026 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Cooper, J. A. & Sept, D. New insights into mechanism and regulation of actin capping protein. Int. Rev. Cell. Mol. Biol. 267, 183–206 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Carlier, M. F. et al. Actin depolymerizing factor (ADF/cofilin) enhances the rate of filament turnover: implication in actin-based motility. J. Cell Biol. 136, 1307–1322 (1997).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Wachsstock, D. H., Schwarz, W. H. & Pollard, T. D. Cross-linker dynamics determine the mechanical properties of actin gels. Biophys. J. 66, 801–809 (1994).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  24. Hsiung, F., Ramirez-Weber, F. A., Iwaki, D. D. & Kornberg, T. B. Dependence of Drosophila wing imaginal disc cytonemes on Decapentaplegic. Nature 437, 560–563 (2005).

    Article  ADS  PubMed  CAS  Google Scholar 

  25. Liu, A. P. et al. Membrane-induced bundling of actin filaments. Nature Phys. 4, 789–793 (2008).

    Article  ADS  CAS  Google Scholar 

  26. Janmey, P. A. & McCulloch, C. A. Cell mechanics: integrating cell responses to mechanical stimuli. Annu. Rev. Biomed. Eng. 9, 1–34 (2007).

    Article  PubMed  CAS  Google Scholar 

  27. Campellone, K. G., Webb, N. J., Znameroski, E. A. & Welch, M. D. WHAMM is an Arp2/3 complex activator that binds microtubules and functions in ER to Golgi transport. Cell 134, 148–161 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K. & Salmon, E. D. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nature Cell Biol. 1, 45–50 (1999).

    Article  PubMed  CAS  Google Scholar 

  29. MacKintosh, F. C., Kas, J. & Janmey, P. A. Elasticity of semiflexible biopolymer networks. Phys. Rev. Lett. 75, 4425–4428 (1995).

    Article  ADS  PubMed  CAS  Google Scholar 

  30. Storm, C., Pastore, J. J., MacKintosh, F. C., Lubensky, T. C. & Janmey, P. A. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005). In this study, the role of entropic elasticity was shown experimentally and modelled for a broad set of cytoskeletal polymers.

    Article  ADS  PubMed  CAS  Google Scholar 

  31. Gardel, M. L. et al. Elastic behavior of cross-linked and bundled actin networks. Science 304, 1301–1305 (2004).

    Article  ADS  PubMed  CAS  Google Scholar 

  32. Tharmann, R., Claessens, M. M. & Bausch, A. R. Viscoelasticity of isotropically cross-linked actin networks. Phys. Rev. Lett. 98, 088103 (2007).

  33. Koenderink, G. H. et al. An active biopolymer network controlled by molecular motors. Proc. Natl Acad. Sci. USA 106, 15192–15197 (2009).

    Article  ADS  PubMed  Google Scholar 

  34. Chaudhuri, O., Parekh, S. H. & Fletcher, D. A. Reversible stress softening of actin networks. Nature 445, 295–298 (2007). This paper showed that the architecture of actin-filament networks affects the relative importance of entropic and enthalpic elasticity.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  35. Wagner, B., Tharmann, R., Haase, I., Fischer, M. & Bausch, A. R. Cytoskeletal polymer networks: the molecular structure of cross-linkers determines macroscopic properties. Proc. Natl Acad. Sci. USA 103, 13974–13978 (2006).

    Article  ADS  PubMed  CAS  Google Scholar 

  36. Herant, M., Heinrich, V. & Dembo, M. Mechanics of neutrophil phagocytosis: behavior of the cortical tension. J. Cell Sci. 118, 1789–1797 (2005).

    Article  PubMed  CAS  Google Scholar 

  37. Charras, G. T., Yarrow, J. C., Horton, M. A., Mahadevan, L. & Mitchison, T. J. Non-equilibration of hydrostatic pressure in blebbing cells. Nature 435, 365–369 (2005).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  38. Wang, N., Tytell, J. D. & Ingber, D. E. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nature Rev. Mol. Cell Biol. 10, 75–82 (2009).

    Article  CAS  Google Scholar 

  39. Basu, A., Joanny, J. F., Julicher, F. & Prost, J. Thermal and non-thermal fluctuations in active polar gels. Eur. Phys. J. E 27, 149–160 (2008).

    Article  PubMed  CAS  Google Scholar 

  40. Bursac, P. et al. Cytoskeletal remodelling and slow dynamics in the living cell. Nature Mater. 4, 557–561 (2005).

    Article  ADS  CAS  Google Scholar 

  41. Keren, K. et al. Mechanism of shape determination in motile cells. Nature 453, 475–480 (2008).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  42. Dogterom, M. & Yurke, B. Measurement of the force–velocity relation for growing microtubules. Science 278, 856–860 (1997).

    Article  ADS  PubMed  CAS  Google Scholar 

  43. Footer, M. J., Kerssemakers, J. W., Theriot, J. A. & Dogterom, M. Direct measurement of force generation by actin filament polymerization using an optical trap. Proc. Natl Acad. Sci. USA 104, 2181–2186 (2007).

    Article  ADS  PubMed  CAS  Google Scholar 

  44. Parekh, S. H., Chaudhuri, O., Theriot, J. A. & Fletcher, D. A. Loading history determines the velocity of actin-network growth. Nature Cell Biol. 7, 1219–1223 (2005).

    Article  PubMed  CAS  Google Scholar 

  45. Prass, M., Jacobson, K., Mogilner, A. & Radmacher, M. Direct measurement of the lamellipodial protrusive force in a migrating cell. J. Cell Biol. 174, 767–772 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Janmey, P. A., Winer, J. P., Murray, M. E. & Wen, Q. The hard life of soft cells. Cell. Motil. Cytoskeleton 66, 597–605 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Discher, D. E., Janmey, P. & Wang, Y. L. Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139–1143 (2005).

    Article  ADS  PubMed  CAS  Google Scholar 

  48. Chen, C. S. Mechanotransduction — a field pulling together? J. Cell Sci. 121, 3285–3292 (2008).

    Article  PubMed  CAS  Google Scholar 

  49. Thery, M. et al. The extracellular matrix guides the orientation of the cell division axis. Nature Cell Biol. 7, 947–953 (2005).

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  51. Cheng, G., Tse, J., Jain, R. K. & Munn, L. L. Micro-environmental mechanical stress controls tumor spheroid size and morphology by suppressing proliferation and inducing apoptosis in cancer cells. PLoS ONE 4, e4632 (2009).

  52. Paszek, M. J. et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 8, 241–254 (2005).

    Article  PubMed  CAS  Google Scholar 

  53. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006). This paper showed that substrate elasticity can control the differentiation of mesenchymal stem cells.

    Article  PubMed  CAS  Google Scholar 

  54. Saha, K. et al. Substrate modulus directs neural stem cell behavior. Biophys. J. 95, 4426–4438 (2008).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  55. Discher, D. E., Mooney, D. J. & Zandstra, P. W. Growth factors, matrices, and forces combine and control stem cells. Science 324, 1673–1677 (2009).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  56. Berdyyeva, T. K., Woodworth, C. D. & Sokolov, I. Human epithelial cells increase their rigidity with ageing in vitro: direct measurements. Phys. Med. Biol. 50, 81–92 (2005).

    Article  PubMed  Google Scholar 

  57. Burns, J. M., Cuschieri, A. & Campbell, P. A. Optimisation of fixation period on biological cells via time-lapse elasticity mapping. Jpn. J. Appl. Phys. 45, 2341–2344 (2006).

    Article  ADS  CAS  Google Scholar 

  58. Kato, S. et al. Characterization and phenotypic variation with passage number of cultured human endometrial adenocarcinoma cells. Tissue Cell 40, 95–102 (2008).

    Article  PubMed  CAS  Google Scholar 

  59. Sawada, Y. et al. Force sensing by mechanical extension of the Src family kinase substrate p130Cas . Cell 127, 1015–1026 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Mammoto, A. et al. A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457, 1103–1108 (2009).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  61. Weiss, P. A. Principles of Development; A Text in Experimental Embryology (H. Holt, 1939).

    Google Scholar 

  62. Sonneborn, T. M. The differentiation of cells. Proc. Natl Acad. Sci. USA 51, 915–929 (1964).

    Article  ADS  PubMed  CAS  Google Scholar 

  63. Beisson, J. & Sonneborn, T. M. Cytoplasmic inheritance of organization of cell cortex in Paramecium aurelia . Proc. Natl Acad. Sci. USA 53, 275–282 (1965).

    Article  ADS  PubMed  CAS  Google Scholar 

  64. Albrecht-Buehler, G. Phagokinetic tracks of 3T3 cells: parallels between the orientation of track segments and of cellular structures which contain actin or tubulin. Cell 12, 333–339 (1977).

    Article  PubMed  CAS  Google Scholar 

  65. Albrecht-Buehler, G. Daughter 3T3 cells. Are they mirror images of each other? J. Cell Biol. 72, 595–603 (1977).

    Article  PubMed  CAS  Google Scholar 

  66. Delhanty, P., Leung, H. & Locke, M. Paired cytoskeletal patterns in an epithelium of siamese twin cells. Eur. J. Cell Biol. 56, 443–450 (1991).

    PubMed  CAS  Google Scholar 

  67. Anderson, C. T. & Stearns, T. Centriole age underlies asynchronous primary cilium growth in mammalian cells. Curr. Biol. 19, 1498–1502 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Sato, M., Levesque, M. J. & Nerem, R. M. Micropipette aspiration of cultured bovine aortic endothelial cells exposed to shear stress. Arteriosclerosis 7, 276–286 (1987).

    Article  PubMed  CAS  Google Scholar 

  69. Janmey, P. A. The cytoskeleton and cell signaling: component localization and mechanical coupling. Physiol. Rev. 78, 763–781 (1998).

    Article  PubMed  CAS  Google Scholar 

  70. Locke, M. Is there somatic inheritance of intracellular patterns? J. Cell Sci. 96, 563–567 (1990). This paper summarized early examples of 'cytoskeletal epigenetics'.

    Google Scholar 

  71. Kaksonen, M., Toret, C. P. & Drubin, D. G. A modular design for the clathrin- and actin-mediated endocytosis machinery. Cell 123, 305–320 (2005).

    Article  PubMed  CAS  Google Scholar 

  72. Ganem, N. J., Godinho, S. A. & Pellman, D. A mechanism linking extra centrosomes to chromosomal instability. Nature 460, 278–282 (2009).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  73. Omary, M. B., Coulombe, P. A. & McLean, W. H. Intermediate filament proteins and their associated diseases. N. Engl. J. Med. 351, 2087–2100 (2004).

    Article  PubMed  CAS  Google Scholar 

  74. Fygenson, D. K., Elbaum, M., Shraiman, B. & Libchaber, A. Microtubules and vesicles under controlled tension. Phys. Rev. E 55, 850–859 (1997).

    Article  ADS  Google Scholar 

  75. Pontani, L. L. et al. Reconstitution of an actin cortex inside a liposome. Biophys. J. 96, 192–198 (2009).

    Article  ADS  PubMed  CAS  Google Scholar 

  76. Liu, A. P. & Fletcher, D. A. Biology under construction: in vitro reconstitution of cellular function. Nature Rev. Mol. Cell Biol. 10, 644–650 (2009).

    Article  CAS  Google Scholar 

  77. Jones, L. J., Carballido-Lopez, R. & Errington, J. Control of cell shape in bacteria: helical, actin-like filaments in Bacillus subtilis . Cell 104, 913–922 (2001).

    Article  PubMed  CAS  Google Scholar 

  78. Ausmees, N., Kuhn, J. R. & Jacobs-Wagner, C. The bacterial cytoskeleton: an intermediate filament-like function in cell shape. Cell 115, 705–713 (2003).

    Article  PubMed  CAS  Google Scholar 

  79. Garner, E. C., Campbell, C. S. & Mullins, R. D. Dynamic instability in a DNA-segregating prokaryotic actin homolog. Science 306, 1021–1025 (2004).

    Article  ADS  PubMed  CAS  Google Scholar 

  80. Garner, E. C., Campbell, C. S., Weibel, D. B. & Mullins, R. D. Reconstitution of DNA segregation driven by assembly of a prokaryotic actin homolog. Science 315, 1270–1274 (2007).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  81. Derman, A. I. et al. Phylogenetic analysis identifies many uncharacterized actin-like proteins (Alps) in bacteria: regulated polymerization, dynamic instability and treadmilling in Alp7A. Mol. Microbiol. 73, 534–552 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Rochlin, M. W., Dailey, M. E. & Bridgman, P. C. Polymerizing microtubules activate site-directed F-actin assembly in nerve growth cones. Mol. Biol. Cell 10, 2309–2327 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Henson, J. H. et al. Two components of actin-based retrograde flow in sea urchin coelomocytes. Mol. Biol. Cell 10, 4075–4090 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Svitkina, T. M. et al. Mechanism of filopodia initiation by reorganization of a dendritic network. J. Cell Biol. 160, 409–421 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Stossel, T. P. et al. Filamins as integrators of cell mechanics and signalling. Nature Rev. Mol. Cell Biol. 2, 138–145 (2001).

    Article  CAS  Google Scholar 

  86. Svitkina, T. M., Verkhovsky, A. B. & Borisy, G. G. Improved procedures for electron microscopic visualization of the cytoskeleton of cultured cells. J. Struct. Biol. 115, 290–303 (1995).

    Article  PubMed  CAS  Google Scholar 

  87. Chaudhuri, O., Parekh, S. H., Lam, W. A. & Fletcher, D. A. Combined atomic force microscopy and side-view optical imaging for mechanical studies of cells. Nature Methods 6, 383–387 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Stachowiak, J. C. et al. Unilamellar vesicle formation and encapsulation by microfluidic jetting. Proc. Natl Acad. Sci. USA 105, 4697–4702 (2008).

    Article  ADS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank O. Chaudhuri, D. Richmond, V. Risca and other members of the Fletcher laboratory for discussion and assistance with this Review. We also benefited from interactions with the researchers and students in the 2009 Physiology course at the Marine Biological Laboratory, Woods Hole, Massachusetts. Work in our laboratories is supported by R01 grants from the National Institutes of Health (NIH) and by the Cell Propulsion Lab, an NIH Nanomedicine Development Center. We apologize to those colleagues whose work could not be cited because of space constraints.

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Reprints and permissions information is available at htpp://www.nature.com/reprints.

Correspondence should be addressed to D.A.F. (fletch@berkeley.edu) or R.D.M. (dyche@mullinslab.ucsf.edu).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fletcher, D., Mullins, R. Cell mechanics and the cytoskeleton. Nature 463, 485–492 (2010). https://doi.org/10.1038/nature08908

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature08908

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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