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:

Forcing cells into shape: the mechanics of actomyosin contractility

Nature Reviews Molecular Cell Biology volume 16, pages 486–498 (2015)Cite this article

Subjects

Key Points

  • The capability of cells to generate contractile forces originates from the activity of the molecular motor myosin II on its substrate actin filaments.

  • Although the molecular constituents of contractility are well conserved across cell types, the organization of myosin and actin filaments varies widely from highly organized sarcomeres in striated muscle to non-sarcomeric organizations in smooth and non-muscle cells.

  • In sarcomeres, actomyosin geometry regulates force transmission and is well understood. The non-sarcomeric organiazations of actomyosin require novel mechanisms of force transmission, from molecular to cellular length scales, and alternative mechanisms of contractility.

  • Alternativee mechanisms of force transmission invoke nonlinear response of actin filaments and spatial localization of actin filament assembly.

  • Non-sarcomeric actomyosin assemblies facilitate large shape changes, and mechanochemical feedback exists to coordinate assembly dynamics with contractility.

  • Actomyosin networks are also used in cell mechanosensing and facilitate a novel mode of intracellular transport.

Abstract

Actomyosin-mediated contractility is a highly conserved mechanism for generating mechanical stress in animal cells and underlies muscle contraction, cell migration, cell division and tissue morphogenesis. Whereas actomyosin-mediated contractility in striated muscle is well understood, the regulation of such contractility in non-muscle and smooth muscle cells is less certain. Our increased understanding of the mechanics of actomyosin arrays that lack sarcomeric organization has revealed novel modes of regulation and force transmission. This work also provides an example of how diverse mechanical behaviours at cellular scales can arise from common molecular components, underscoring the need for experiments and theories to bridge the molecular to cellular length scales.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1: Types of contractile deformations generated by cells and tissues.
Figure 2: Contractility in sarcomeres.
Figure 3: Contractility in disordered actomyosin bundles.
Figure 4: Inherent contractility of adherent cells.

Similar content being viewed by others

References

  1. Munjal, A. & Lecuit, T. Actomyosin networks and tissue morphogenesis. Development 141, 1789–1793 (2014).

    Article  CAS  PubMed  Google Scholar 

  2. Gardel, M. L., Schneider, I. C., Aratyn-Schaus, Y. & Waterman, C. M. Mechanical integration of actin and adhesion dynamics in cell migration. Annu. Rev. Cell Dev. Biol. 26, 315–333 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Vicente-Manzanares, M., Ma, X., Adelstein, R. S. & Horwitz, A. R. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat. Rev. Mol. Cell Biol. 10, 778–790 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Salbreux, G., Charras, G. & Paluch, E. Actin cortex mechanics and cellular morphogenesis. Trends Cell Biol. 10, 536–545 (2012).

    Google Scholar 

  5. Green, R. A., Paluch, E. & Oegema, K. Cytokinesis in animal cells. Annu. Rev. Cell Dev. Biol. 28, 29–58 (2012).

    CAS  PubMed  Google Scholar 

  6. Pinto, I. M. et al. Actin depolymerization drives actomyosin ring contraction during budding yeast cytokinesis. Dev. Cell 22, 1247–1260 (2012).

    PubMed Central  Google Scholar 

  7. Murrell, M. P. et al. Liposome adhesion generates traction stress. Nat. Phys. 10, 163–169 (2014).

    CAS  Google Scholar 

  8. Stroka, K. M. et al. Water permeation drives tumor cell migration in confined microenvironments. Cell 157, 611–623 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Levayer, R. & Lecuit, T. Biomechanical regulation of contractility: spatial control and dynamics. Trends Cell Biol. 22, 61–81 (2012).

    PubMed  Google Scholar 

  10. Lecuit, T., Lenne, P.-F. & Munro, E. Force generation, transmission, and integration during cell and tissue morphogenesis. Ann. Rev. Cell Dev. Bio 27, 157–184 (2011).

    CAS  Google Scholar 

  11. Gordon, A. M., Homsher, E. & Regnier, M. Regulation of contraction in striated muscle. Physiol. Rev. 80, 853–924 (2000).

    CAS  PubMed  Google Scholar 

  12. Huxley, H. E. Fifty years of muscle and the sliding filament hypothesis. Eur. J. Biochem. 271, 1403–1415 (2004).

    CAS  PubMed  Google Scholar 

  13. Steinmetz, P. R. H. et al. Independent evolution of striated muscles in cnidarians and bilaterians. Nature 487, 231–234 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Niederman, R. & Pollard, T. D. Human platelet myosin. II. In vitro assembly and structure of myosin filaments. J. Cell Biol. 67, 72–92 (1975).

    CAS  PubMed  Google Scholar 

  15. Pollard, T. D. Structure and polymerization of Acanthamoeba myosin-II filaments. J. Cell Biol. 95, 816–825 (1982).

    CAS  PubMed  Google Scholar 

  16. Skubiszak, L. & Kowalczyk, L. Myosin molecule packing within the vertebrate skeletal muscle thick filaments. A complete bipolar model. Acta Biochim. Polon. 49, 829–840 (2002).

    CAS  PubMed  Google Scholar 

  17. Sobieszek, A. Cross-bridges on self-assembled smooth muscle myosin filaments. J. Mol. Biol. 70, 741–744 (1972).

    CAS  PubMed  Google Scholar 

  18. Tonino, P., Simon, M. & Craig, R. Mass determination of native smooth muscle myosin filaments by scanning transmission electron microscopy. J. Mol. Biol. 318, 999–1007 (2002).

    CAS  PubMed  Google Scholar 

  19. Huxley, H. E. X-ray analysis and the problem of muscle. Proc. R. Soc. Lond. B 141, 59–62 (1953).

    CAS  PubMed  Google Scholar 

  20. Huxley, H. E. The double array of filaments in cross-striated muscle. J. Biophys. Biochem. Cytol. 3, 631–648 (1957).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Huxley, A. F. Muscle structure and theories of contraction. Prog. Biophys. Biophys. Chem. 7, 255–318 (1957).

    CAS  PubMed  Google Scholar 

  22. Huxley, A. F. & Niedergerke, R. Structural changes in muscle during contraction: interference microscopy of living muscle fibres. Nature 173, 971–973 (1954).

    CAS  PubMed  Google Scholar 

  23. Littlefield, R., Almenar-Queralt, A. & Fowler, V. M. Actin dynamics at pointed ends regulates thin filament length in striated muscle. Nat. Cell Biol. 3, 544–551 (2001).

    CAS  PubMed  Google Scholar 

  24. Lavoie, T. L. et al. Disrupting actin–myosin–actin connectivity in airway smooth muscle as a treatment for asthma? Proc. Am. Thorac. Soc. 6, 295–300 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Gunst, S. J. & Zhang, W. Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction. Am. J. Physiol. Cell Physiol. 295, C576–587 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Verkhovsky, A. B. & Borisy, G. G. Non-sarcomeric mode of myosin II organization in the fibroblast lamellum. J. Cell Biol. 123, 637–652 (1993).

    CAS  PubMed  Google Scholar 

  27. Svitkina, T. M., Verkhovsky, A. B., McQuade, K. M. & Borisy, G. G. Analysis of the actin–myosin II system in fish epidermal keratocytes: mechanism of cell body translocation. J. Cell Biol. 139, 397–415 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Aratyn-Schaus, Y., Oakes, P. W. & Gardel, M. L. Dynamic and structural signatures of lamellar actomyosin force generation. Mol. Biol. Cell 22, 1330–1339 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Hotulainen, P. & Lappalainen, P. Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J. Cell Biol. 173, 383–394 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Svitkina, T. M. & Borisy, G. G. Correlative light and electron microscopy of the cytoskeleton of cultured cells. Methods Enzymol. 298, 570–592 (1998).

    CAS  PubMed  Google Scholar 

  31. Stricker, J., Beckham, Y., Davidson, M. W. & Gardel, M. L. Myosin II-mediated focal adhesion maturation is tension insensitive. PLoS ONE 8, e70652 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Oakes, P. W., Beckham, Y., Stricker, J. & Gardel, M. L. Tension is required but not sufficient for focal adhesion maturation without a stress fiber template. J. Cell Bio. 196, 363–374 (2012).

    CAS  Google Scholar 

  33. Martin, A. C. et al. Integration of contractile forces during tissue invagination. J. Cell Biol. 188, 735–749 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Martin, A. C., Kaschube, M. & Wieschaus, E. F. Pulsed contractions of an actin–myosin network drive apical constriction. Nature 457, 495–499 (2009).

    CAS  PubMed  Google Scholar 

  35. He, L., Wang, X., Tang, H. L. & Montell, D. J. Tissue elongation requires oscillating contractions of a basal actomyosin network. Nat. Cell Biol. 12, 1133–1142 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Levayer, R. & Lecuit, T. Oscillation and polarity of E-cadherin asymmetries control actomyosin flow patterns during morphogenesis. Dev. Cell 26, 162–175 (2013).

    CAS  PubMed  Google Scholar 

  37. Kim, T., Gardel, M. L. & Munro, E. Determinants of fluidlike behavior and effective viscosity in cross-linked actin networks. Biophys. J. 106, 526–534 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Courtemanche, N., Lee, J. Y., Pollard, T. D. & Greene, E. C. Tension modulates actin filament polymerization mediated by formin and profilin. Proc. Natl Acad. Sci. USA 110, 9752–9757 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Ferrer, J. M. et al. Measuring molecular rupture forces between single actin filaments and actin-binding proteins. Proc. Natl Acad. Sci. USA 105, 9221–9226 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Jégou, A., Carlier, M.-F. & Romet-Lemonne, G. Formin mDia1 senses and generates mechanical forces on actin filaments. Nat. Commun. 4, 1883 (2013).

    PubMed  Google Scholar 

  41. Wilson, C. A. et al. Myosin II contributes to cell-scale actin network treadmilling through network disassembly. Nature 465, 373–377 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Fritzsche, M. et al. Analysis of turnover dynamics of the submembranous actin cortex. Mol. Biol. Cell 24, 757–767 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Carvalho, A., Desai, A. & Oegema, K. Structural memory in the contractile ring makes the duration of cytokinesis independent of cell size. Cell 137, 926–937 (2009).

    CAS  PubMed  Google Scholar 

  44. Luo, W. et al. Analysis of the local organization and dynamics of cellular actin networks. J. Cell Biol. 202, 1057–1073 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Lenz, M., Gardel, M. L. & Dinner, A. R. Requirements for contractility in disordered cytoskeletal bundles. New J. Phys. 14, 033037 (2012).

    PubMed  PubMed Central  Google Scholar 

  46. Vavylonis, D. et al. Assembly mechanism of the contractile ring for cytokinesis by fission yeast. Science 319, 97–100 (2008).

    CAS  PubMed  Google Scholar 

  47. Kruse, K. & Julicher, F. Actively contracting bundles of polar filaments. Phys. Rev. Lett. 85, 1778–1781 (2000).

    CAS  PubMed  Google Scholar 

  48. Liverpool, T. B. & Marchetti, M. C. Bridging the microscopic and the hydrodynamic in active filament solutions. Europhys. Lett. 69, 846 (2005).

    CAS  Google Scholar 

  49. Tsuda, Y., Yasutake, H., Ishijima, A. & Yanagida, T. Torsional rigidity of single actin filaments and actin–actin bond breaking force under torsion measured directly by in vitro micromanipulation. Proc. Natl Acad. Sci. USA 93, 12937–12942 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. McCullough, B. R. et al. Cofilin-linked changes in actin filament flexibility promote severing. Biophys. J. 101, 151–159 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Arai, Y. et al. Tying a molecular knot with optical tweezers. Nature 399, 446–448 (1999).

    CAS  PubMed  Google Scholar 

  52. Lenz, M., Thoresen, T., Gardel, M. L. & Dinner, A. R. Contractile units in disordered actomyosin bundles arise from F-actin buckling. Phys. Rev. Lett. 108, 238107 (2012).

    PubMed  PubMed Central  Google Scholar 

  53. Murrell, M. P. & Gardel, M. L. F-actin buckling coordinates contractility and severing in a biomimetic actomyosin cortex. Proc. Natl Acad. Sci. USA 51, 20820–20825 (2012).

    Google Scholar 

  54. Hayakawa, K., Tatsumi, H. & Sokabe, M. Actin filaments function as a tension sensor by tension-dependent binding of cofilin to the filament. J. Cell Biol. 195, 721–727 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Vogel, S. K., Petrasek, Z., Heinemann, F. & Schwille, P. Myosin motors fragment and compact membrane-bound actin filaments. eLife 2, e00116 (2013).

    PubMed  PubMed Central  Google Scholar 

  56. Lenz, M. Geometrical origins of contractility in disordered actomyosin networks. Phys. Rev. X 4, 041002 (2014).

    Google Scholar 

  57. Thoresen, T., Lenz, M. & Gardel, M. L. Thick filament length and isoform composition determine self-organized contractile units in actomyosin bundles. Biophys. J. 104, 655–665 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Haviv, L., Gillo, D., Backouche, F. & Bernheim-Groswasser, A. A cytoskeletal demolition worker: myosin II acts as an actin depolymerization agent. J. Mol. Biol. 375, 325–330 (2008).

    CAS  PubMed  Google Scholar 

  59. Pelham, R. J. & Chang, F. Actin dynamics in the contractile ring during cytokinesis in fission yeast. Nature 419, 82–86 (2002).

    CAS  PubMed  Google Scholar 

  60. Costa, K. D., Hucker, W. J. & Yin, F. C. Buckling of actin stress fibers: a new wrinkle in the cytoskeletal tapestry. Cell. Motil. Cytoskeleton 52, 266–274 (2002).

    PubMed  Google Scholar 

  61. Heissler, S. M. & Manstein, D. J. Nonmuscle myosin-2: mix and match. Cell. Mol. Life Sci. 70, 1–21 (2013).

    CAS  PubMed  Google Scholar 

  62. Parsons, J. T., Horwitz, A. R. & Schwartz, M. A. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat. Rev. Mol. Cell Biol. 11, 633–643 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Jordan, S. N. & Canman, J. C. Rho GTPases in animal cell cytokinesis: an occupation by the one percent. Cytoskeleton 69, 919–930 (2012).

    CAS  PubMed  Google Scholar 

  64. Machacek, M. et al. Coordination of Rho GTPase activities during cell protrusion. Nature 461, 99–103 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Munro, E. & Bowerman, B. Cellular symmetry breaking during Caenorhabditis elegans development. Cold Spring Harb. Perspect. Biol. 1, a003400 (2009).

    PubMed  PubMed Central  Google Scholar 

  66. Janson, L. W., Kolega, J. & Taylor, D. L. Modulation of contraction by gelation/solation in a reconstituted motile model. J. Cell Biol. 114, 1005–1015 (1991).

    CAS  PubMed  Google Scholar 

  67. Bendix, P. M. et al. A quantitative analysis of contractility in active cytoskeletal protein networks. Biophys. J. 94, 3126–3136 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Thoresen, T., Lenz, M. & Gardel, M. L. Reconstitution of contractile actomyosin bundles. Biophys. J. 100, 2698–2705 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Alvarado, J. et al. Molecular motors robustly drive active gels to a critically connected state. Nat. Phys. 9, 591–597 (2013).

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  71. Kasza, K. E. et al. Nonlinear elasticity of stiff biopolymers connected by flexible linkers. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 79, 041928 (2009).

    CAS  PubMed  Google Scholar 

  72. Kohler, S., Schaller, V. & Bausch, A. R. Structure formation in active networks. Nat. Mater. 10, 462–468 (2011).

    PubMed  Google Scholar 

  73. Reymann, A.-C. et al. Nucleation geometry governs ordered actin networks structures. Nat. Mater. 9, 827–832 (2010).

    CAS  PubMed  Google Scholar 

  74. Alexandrova, A. Y. et al. Comparative dynamics of retrograde actin flow and focal adhesions: formation of nascent adhesions triggers transition from fast to slow flow. PLoS ONE 3, e3234 (2008).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Gardel, M. L. et al. Prestressed F-actin networks cross-linked by hinged filamins replicate mechanical properties of cells. Proc. Natl Acad. Sci. USA 103, 1762–1767 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Smith, M. A. et al. A zyxin-mediated mechanism for actin stress fiber maintenance and repair. Dev. Cell 19, 365–376 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Halder, G., Dupont, S. & Piccolo, S. Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat. Rev. Mol. Cell Biol. 13, 591–600 (2012).

    CAS  PubMed  Google Scholar 

  79. Cowan, C. R. & Hyman, A. A. Acto-myosin reorganization and PAR polarity in C. elegans. Development 134, 1035–1043 (2007).

    CAS  PubMed  Google Scholar 

  80. Liu, C. et al. Actin-mediated feedback loops in B-cell receptor signaling. Immunol. Rev. 256, 177–189 (2013).

    PubMed  Google Scholar 

  81. Storm, C. et al. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005).

    CAS  PubMed  Google Scholar 

  82. Gardel, M. L. et al. Stress-dependent elasticity of composite actin networks as a model for cell behavior. Phys. Rev. Lett. 96, 088102 (2006).

    CAS  PubMed  Google Scholar 

  83. Kasza, K. E. et al. Filamin A is essential for active cell stiffening but not passive stiffening under external force. Biophys. J. 96, 4326–4335 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Mizuno, D., Tardin, C., Schmidt, C. F. & Mackintosh, F. C. Nonequilibrium mechanics of active cytoskeletal networks. Science 315, 370–373 (2007).

    CAS  PubMed  Google Scholar 

  85. Pasternak, C., Spudich, J. A. & Elson, E. L. Capping of surface receptors and concomitant cortical tension are generated by conventional myosin. Nature 341, 549–551 (1989).

    CAS  PubMed  Google Scholar 

  86. Wang, N. et al. Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells. Am. J. Physiol. Cell Physiol. 282, C606–616 (2002).

    CAS  PubMed  Google Scholar 

  87. Stamenovic, D., Liang, Z., Chen, J. & Wang, N. Effect of the cytoskeletal prestress on the mechanical impedance of cultured airway smooth muscle cells. J. Appl. Physiol. 92, 1443–1450 (2002).

    PubMed  Google Scholar 

  88. Balland, M., Richert, A. & Gallet, F. The dissipative contribution of myosin II in the cytoskeleton dynamics of myoblasts. Eur. Biophys. J. 34, 255–261 (2005).

    CAS  PubMed  Google Scholar 

  89. Martens, J. C. & Radmacher, M. Softening of the actin cytoskeleton by inhibition of myosin II. Pflugers Arch. 456, 95–100 (2008).

    CAS  PubMed  Google Scholar 

  90. Lau, A. W. et al. Microrheology, stress fluctuations, and active behavior of living cells. Phys. Rev. Lett. 91, 198101 (2003).

    CAS  PubMed  Google Scholar 

  91. 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  PubMed Central  Google Scholar 

  92. Fakhri, N. et al. High-resolution mapping of intracellular fluctuations using carbon nanotubes. Science 344, 1031–1035 (2014).

    CAS  PubMed  Google Scholar 

  93. Manneville, J. B., Bassereau, P., Levy, D. & Prost, J. Activity of transmembrane proteins induces magnification of shape fluctuations of lipid membranes. Phys. Rev. Lett. 82, 4356–4359 (1999).

    CAS  Google Scholar 

  94. Betz, T., Lenz, M., Joanny, J. F. & Sykes, C. ATP-dependent mechanics of red blood cells. Proc. Natl Acad. Sci. USA 106, 15320–15325 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. le Duc, Q. et al. Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J. Cell Biol. 189, 1107–1115 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Heisenberg, C.-P. & Bellaïche, Y. Forces in tissue morphogenesis and patterning. Cell 153, 948–962 (2013).

    CAS  PubMed  Google Scholar 

  97. Sonnemann, K. J. & Bement, W. M. Wound repair: toward understanding and integration of single-cell and multicellular wound responses. Annu. Rev. Cell Dev. Biol. 27, 237–263 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Friedl, P. & Gilmour, D. Collective cell migration in morphogenesis, regeneration and cancer. Nat. Rev. Mol. Cell Biol. 10, 445–457 (2009).

    CAS  PubMed  Google Scholar 

  99. Sedzinski, J. et al. Polar actomyosin contractility destabilizes the position of the cytokinetic furrow. Nature 476, 462–466 (2011).

    CAS  PubMed  Google Scholar 

  100. Tinevez, J.-Y. et al. Role of cortical tension in bleb growth. Proc. Natl Acad. Sci. 106, 18581–18586 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Rubinstein, B. et al. Actin–myosin viscoelastic flow in the keratocyte lamellipod. Biophys. J. 97, 1853–1863 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Kruse, K., Joanny, J. F., Julicher, F. & Prost, J. Contractility and retrograde flow in lamellipodium motion. Phys. Biol. 3, 130–137 (2006).

    CAS  PubMed  Google Scholar 

  103. Mertz, A. F. et al. Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces. Proc. Natl Acad. Sci. USA 110, 842–847 (2012).

    PubMed  PubMed Central  Google Scholar 

  104. Goehring, N. W. et al. Polarization of PAR proteins by advective triggering of a pattern-forming system. Science 334, 1137–1141 (2011).

    CAS  PubMed  Google Scholar 

  105. Oakes, P. W., Banerjee, S., Marchetti, M. C. & Gardel, M. L. Geometry regulates traction stresses in adherent cells. Biophys. J. 107, 825–833 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Guthardt Torres, P., Bischofs, I. B. & Schwarz, U. S. Contractile network models for adherent cells. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 85, 011913 (2012).

    CAS  PubMed  Google Scholar 

  107. Howard, J. Mechanics of Motor Proteins and the Cytoskeleton (Sinauer Associates, 2001).

    Google Scholar 

  108. Yao, Norman, Y. et al. Stress-enhanced gelation: A dynamic nonlinearity of elasticity. Phys. Rev. Lett. 110, 018103 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Verkhovsky, A. B., Svitkina, T. M. & Borisy, G. G. Self-polarization and directional motility of cytoplasm. Curr. Biol. 9, 11–20 (1999).

    CAS  PubMed  Google Scholar 

  110. Sun, S. X., Walcott, S. & Wolgemuth, C. W. Cytoskeletal cross-linking and bundling in motor-independent contraction. Curr. Biol. 20, R649–R654 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Ramaswamy, S. The mechanics and statistics of active matter. Annu. Rev. Condensed Matter Phys. 1, 323–345 (2010).

    Google Scholar 

  112. Bartles, J. R. Parallel actin bundles and their multiple actin-bundling proteins. Curr. Opin. Cell Biol. 12, 72–78 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Kohler, S. & Bausch, A. R. Contraction mechanisms in composite active actin networks. PLoS ONE 7, e39869 (2012).

    PubMed  PubMed Central  Google Scholar 

  114. Kane, R. E. Interconversion of structural and contractile actin gels by insertion of myosin during assembly. J. Cell Biol. 97, 1745–1752 (1983).

    CAS  PubMed  Google Scholar 

  115. Backouche, F., Haviv, L., Groswasser, D. & Bernheim-Groswasser, A. Active gels: dynamics of patterning and self-organization. Phys. Biol. 3, 264–273 (2006).

    CAS  PubMed  Google Scholar 

  116. Aratyn, Y. S., Schaus, T. E., Taylor, E. W. & Borisy, G. G. Intrinsic dynamic behavior of fascin in filopodia. Mol. Biol. Cell 18, 3928–3940 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Wang, K., Ash, J. F. & Singer, S. J. Filamin, a new high-molecular-weight protein found in smooth muscle and non-muscle cells. Proc. Natl Acad. Sci. USA 72, 4483–4486 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Biro, Maté et al. Cell cortex composition and homeostasis resolved by integrating proteomics and quantitative imaging. Cytoskeleton 70, 741–754 (2013).

    CAS  PubMed  Google Scholar 

  119. Schmoller, K. M., Lieleg, O. & Bausch, A. R. Structural and viscoelastic properties of actin/filamin networks: cross-linked versus bundled networks. Biophys. J. 97, 83–89 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Kasza, K. E. et al. Actin filament length tunes elasticity of flexibly cross-linked actin networks. Biophys. J. 99, 1091–1100 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Kohler, S., Schmoller, K. M., Crevenna, A. H. & Bausch, A. R. Regulating contractility of the actomyosin cytoskeleton by pH. Cell Rep. 2, 433–439 (2012).

    PubMed  PubMed Central  Google Scholar 

  122. Goldmann, W. H. & Isenberg, G. Analysis of filamin and α-actinin binding to actin by the stopped flow method. FEBS Lett. 336, 408–410 (1993).

    CAS  PubMed  Google Scholar 

  123. Ebashi, S. & Ebashi, F. α-actinin, a new structural protein from striated muscle. I. Preparation and action on actomyosin-ATP interaction. J. Biochem. 58, 7–12 (1965).

    CAS  PubMed  Google Scholar 

  124. Edlund, M., Lotano, M. A. & Otey, C. A. Dynamics of α-actinin in focal adhesions and stress fibers visualized with α-actinin–green fluorescent protein. Cell. Motil. Cytoskeleton 48, 190–200 (2001).

    CAS  PubMed  Google Scholar 

  125. Sanger, J. M., Mittal, B., Pochapin, M. B. & Sanger, J. W. Stress fiber and cleavage furrow formation in living cells microinjected with fluorescently labeled α-actinin. Cell. Motil. Cytoskeleton 7, 209–220 (1987).

    CAS  PubMed  Google Scholar 

  126. Falzone, T. T., Lenz, M., Kovar, D. R. & Gardel, M. L. Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks. Nat. Commun. 3, 861 (2012).

    PubMed  Google Scholar 

  127. Field, C. M. & Alberts, B. M. Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex. J. Cell Biol. 131, 165–178 (1995).

    CAS  PubMed  Google Scholar 

  128. Schaller, V. et al. Crosslinking proteins modulate the self-organization of driven systems. Soft Matter 9, 7229–7233 (2013).

    CAS  Google Scholar 

  129. Kinoshita, M. et al. Self- and actin-templated assembly of Mammalian septins. Dev. Cell 3, 791–802 (2002).

    CAS  PubMed  Google Scholar 

  130. Reichl, E. M. et al. Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics. Curr. Biol. 18, 471–480 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Weber, I. et al. Two-step positioning of a cleavage furrow by cortexillin and myosin II. Curr. Biol. 10, 501–506 (2000).

    CAS  PubMed  Google Scholar 

  132. Yin, H. L. & Stossel, T. P. Control of cytoplasmic actin gel–sol transformation by gelsolin, a calcium-dependent regulatory protein. Nature 281, 583–586 (1979).

    CAS  PubMed  Google Scholar 

  133. Murrell, M. et al. Spreading dynamics of biomimetic actin cortices. Biophys. J. 100, 1400–1409 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Murrell, M. & Gardel, M. L. Actomyosin sliding is attenuated in contractile biomimetic cortices. Mol. Biol. Cell 25, 1845–1853 (2014).

    PubMed  PubMed Central  Google Scholar 

  135. Carvalho, K. et al. Cell-sized liposomes reveal how actomyosin cortical tension drives shape change. Proc. Natl Acad. Sci. USA 110, 16456–16461 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Y. Beckham and B. Hissa for contributing images for Figure 1. M.L.G. is supported by the Packard Foundation, an American Asthma Foundation grant and NSF-MCB 1344203. M.M. is supported by NSF-CMMI 1434095. M.L.'s group belongs to the CNRS consortium CellTiss. M.L. was supported by grants from Université Paris-Sud and CNRS, Marie Curie Integration Grant PCIG12-GA-2012-334053 and “Investissements d'Avenir” LabEx PALM (ANR-10-LABX-0039-PALM). M.L. and M.L.G. were supported by the University of Chicago FACCTS programme. This work was supported by the University of Chicago MRSEC (NSF-DMR 1420709).

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Yale University, New Haven, 06520, Connecticut, USA

    Michael Murrell

  2. Systems Biology Institute, Yale University, West Haven, 06516, Connecticut, USA

    Michael Murrell

  3. Department of Physics, Institute for Biophysical Dynamics and James Franck Institute, University of Chicago, Chicago, 60637, Illinois, USA

    Patrick W. Oakes & Margaret L. Gardel

  4. Université Paris-Sud, CNRS, LPTMS, UMR 8626, Orsay, 91405, France

    Martin Lenz

Authors
  1. Michael Murrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick W. Oakes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Lenz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Margaret L. Gardel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Margaret L. Gardel.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Glossary

Isotropic contraction

Shortening that is uniform in all directions.

Anisotropic stresses

Shortening that is not uniform in all directions.

Z-line

A region at the boundaries of muscle sarcomeres in which the actin filaments are anchored. It appears as a dark transverse line in electron micrographs.

Force–velocity curve

The relationship between the force applied to a motor and the speed at which it moves relative to its substrate.

Myofibril

The structural unit of striated muscle fibres, which is formed from longitudinally joined sarcomeres. Several myofibrils form each fibre.

Unloaded velocity

The speed at which a motor moves under no applied load. Typical unloaded velocities for myosin II motors range from 50–1,000 nm s−1.

Stall force

The applied force that stops the motion of the motor. Typical stall forces for individual molecular motors are 1–10 pN.

Lamella

RHOA-dependent actomyosin organelles in adherent cells. Actomyosin is organized into a variety of contractile bundles and networks and tethered to the matrix by mature focal adhesions.

Transverse arcs

Actomyosin bundles in the lamella that are parallel to the cell periphery and undergo myosin II-dependent retrograde flow towards the cell centre.

Radial stress fibres

Actin bundles tethered at one end to focal adhesions and integrated into transverse arcs along their length and, thus, oriented in a radial fashion with respect to the cell centre on the dorsal surface. Radial stress fibres do not contain myosin II and assemble in a DIA1- and INF2-dependent manner. They are also known as dorsal stress fibres.

Peripheral bundles

Actomyosin bundles found at non-adherent edges of cells that are responsible for cell shape maintenance.

Ventral stress fibres

Actomyosin bundles formed at the ventral surface that are attached to focal adhesions at each end.

Contractile strain

Deformation of a structure that results in shortening of length, area or volume.

Steady-state flow

Movements that occur at a constant rate, or velocity, over time.

Stress relaxation

The decrease of force that occurs in structures owing to viscous, or fluid, effects.

Compressive forces

Force that results in pushing, or compression, on a structure.

Tensile force

Force that results in pulling, or tension, on a structure

Compliance

The tendency of a material to deform in response to an external force. A more compliant material will deform to a greater extent than a less compliant one.

Focal adhesions

Cellular structures that link the extracellular matrix on the outside of the cell, through integrin receptors, to the actin cytoskeleton inside the cell.

Adherens junctions

Protein complexes that contain cadherin and catenin proteins. They are formed between neighbouring cells in the tissue and serve not only to maintain cell–cell adhesion but also to regulate intracellular signalling and cytoskeletal organization.

Elastic response

The tendency of structures to store mechanical energy. The initial shape is preserved upon release of external forces.

Traction force microscopy

A technique to calculate stresses generated by cells by measuring the deformation of the matrix to which they are attached.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murrell, M., Oakes, P., Lenz, M. et al. Forcing cells into shape: the mechanics of actomyosin contractility. Nat Rev Mol Cell Biol 16, 486–498 (2015). https://doi.org/10.1038/nrm4012

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm4012

Search

Advanced 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