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Multiple Roles for Myosin II in Tensional Homeostasis Under Mechanical Loading

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Abstract

Cyclic stretching of adherent cells regulates cell morphology, signal transduction and cell function. It is well established that actin stress fibers are mechano-sensitive structural elements that reorganize in response to applied stress and strain. In this review, we discuss studies revealing the roles of myosin II in stress fiber remodeling including stress fiber assembly, disassembly, and tension maintenance. The results of these studies are interpreted with mathematical models that describe a mechanism by which stress fibers reorganize in response to cyclic stretch and predict how changes in stress fiber tension regulate signal transduction dependent on the spatial and temporal patterns of the applied strain.

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References

  1. Almeida, E. A., D. Ilic, Q. Han, C. R. Hauck, F. Jin, H. Kawakatsu, D. D. Schlaepfer, and C. H. Damsky. Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase. J. Cell Biol. 149:741–754, 2000.

    Article  Google Scholar 

  2. Balaban, N. Q., U. S. Schwarz, D. Riveline, P. Goichberg, G. Tzur, I. Sabanay, D. Mahalu, S. Safran, A. Bershadsky, L. Addadi, and B. Geiger. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3:466–472, 2001.

    Article  Google Scholar 

  3. Bershadsky, A. D., N. Q. Balaban, and B. Geiger. Adhesion-dependent cell mechanosensitivity. Annu. Rev. Cell Dev. Biol. 19:677–695, 2003.

    Article  Google Scholar 

  4. Brown, R. A., R. Prajapati, D. A. McGrouther, I. V. Yannas, and M. Eastwood. Tensional homeostasis in dermal fibroblasts: mechanical responses to mechanical loading in three-dimensional substrates. J. Cell. Physiol. 175:323–332, 1998.

    Article  Google Scholar 

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

    Article  Google Scholar 

  6. Chrzanowska-Wodnicka, M., and K. Burridge. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J. Cell Biol. 133:1403–1415, 1996.

    Article  Google Scholar 

  7. Civelekoglu, G., Y. Tardy, and J. J. Meister. Modeling actin filament reorganization in endothelial cells subjected to cyclic stretch. Bull. Math. Biol. 60:1017–1037, 1998.

    Article  MATH  Google Scholar 

  8. Colombelli, J., A. Besser, H. Kress, E. G. Reynaud, P. Girard, E. Caussinus, U. Haselmann, J. V. Small, U. S. Schwarz, and E. H. Stelzer. Mechanosensing in actin stress fibers revealed by a close correlation between force and protein localization. J. Cell Sci. 122:1665–1679, 2009.

    Article  Google Scholar 

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

    Article  Google Scholar 

  10. Cramer, L. P., M. Siebert, and T. J. Mitchison. Identification of novel graded polarity actin filament bundles in locomoting heart fibroblasts: implications for the generation of motile force. J. Cell Biol. 136:1287–1305, 1997.

    Article  Google Scholar 

  11. De, R., A. Zemel, and S. A. Safran. Dynamics of cell orientation. Nat. Phys. 3:655–659, 2007.

    Article  Google Scholar 

  12. Deguchi, S., T. Ohashi, and M. Sato. Evaluation of tension in actin bundle of endothelial cells based on preexisting strain and tensile properties measurements. Mol. Cell Biomech. 2:125–133, 2005.

    Google Scholar 

  13. DeMali, K. A., K. Wennerberg, and K. Burridge. Integrin signaling to the actin cytoskeleton. Curr. Opin. Cell Biol. 15:572–582, 2003.

    Article  Google Scholar 

  14. Gavara, N., P. Roca-Cusachs, R. Sunyer, R. Farre, and D. Navajas. Mapping cell-matrix stresses during stretch reveals inelastic reorganization of the cytoskeleton. Biophys. J. 95:464–471, 2008.

    Article  Google Scholar 

  15. Goldyn, A. M., B. A. Rioja, J. P. Spatz, C. Ballestrem, and R. Kemkemer. Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding. J. Cell Sci. 122:3644–3651, 2009.

    Article  Google Scholar 

  16. Hahn, C., and M. A. Schwartz. Mechanotransduction in vascular physiology and atherogenesis. Nat. Rev. Mol. Cell Biol. 10:53–62, 2009.

    Article  Google Scholar 

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

    Article  Google Scholar 

  18. Hayakawa, K., N. Sato, and T. Obinata. Dynamic reorientation of cultured cells and stress fibers under mechanical stress from periodic stretching. Exp. Cell Res. 268:104–114, 2001.

    Article  Google Scholar 

  19. Hayakawa, K., H. Tatsumi, and M. Sokabe. Loss of mechanical tension causes ADF/cofilin mediated stress fiber disassembly in cultured endothelial cells: a study by use of a semi-intact cell system. Cell Struct. Funct. 29:S19, 2004.

    Google Scholar 

  20. He, Y., and F. Grinnell. Stress relaxation of fibroblasts activates a cyclic AMP signaling pathway. J. Cell Biol. 126:457–464, 1994.

    Article  Google Scholar 

  21. Hill, A. V. The heat of shortening and the dynamic constants of muscle. Proc. R. Soc. Lond. B Biol. Sci. 126:136–195, 1938.

    Article  Google Scholar 

  22. Hirata, H., H. Tatsumi, and M. Sokabe. Dynamics of actin filaments during tension-dependent formation of actin bundles. Biochim. Biophys. Acta 1115–1127:2007, 1770.

    Google Scholar 

  23. Hirata, H., H. Tatsumi, and M. Sokabe. Mechanical forces facilitate actin polymerization at focal adhesions in a zyxin-dependent manner. J. Cell Sci. 121:2795–2804, 2008.

    Article  Google Scholar 

  24. Hornberger, T. A., D. D. Armstrong, T. J. Koh, T. J. Burkholder, and K. A. Esser. Intracellular signaling specificity in response to uniaxial vs. multiaxial stretch: implications for mechanotransduction. Am. J. Physiol. Cell Physiol. 288:C185–C194, 2005.

    Google Scholar 

  25. Hotulainen, P., and P. Lappalainen. Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J. Cell Biol. 173:383–394, 2006.

    Article  Google Scholar 

  26. Hotulainen, P., E. Paunola, M. K. Vartiainen, and P. Lappalainen. Actin-depolymerizing factor and cofilin-1 play overlapping roles in promoting rapid F-actin depolymerization in mammalian nonmuscle cells. Mol. Biol. Cell 16:649–664, 2005.

    Article  Google Scholar 

  27. Hsu, H. J., C. F. Lee, and R. Kaunas. A dynamic stochastic model of frequency-dependent stress fiber alignment induced by cyclic stretch. PLoS One 4:e4853, 2009.

    Article  Google Scholar 

  28. Hsu, H. J., C. F. Lee, A. Locke, S. Q. Vanderzyl, and R. Kaunas. Stretch-induced stress fiber remodeling and the activations of JNK and ERK depend on mechanical strain rate, but not FAK. PLoS One 5:e12470, 2010.

    Article  Google Scholar 

  29. Jungbauer, S., H. Gao, J. P. Spatz, and R. Kemkemer. Two characteristic regimes in frequency-dependent dynamic reorientation of fibroblasts on cyclically stretched substrates. Biophys. J. 95:3470–3478, 2008.

    Article  Google Scholar 

  30. Katoh, K., Y. Kano, M. Amano, K. Kaibuchi, and K. Fujiwara. Stress fiber organization regulated by MLCK and Rho-kinase in cultured human fibroblasts. Am. J. Physiol. Cell Physiol. 280:C1669–C1679, 2001.

    Google Scholar 

  31. Katsumi, A., T. Naoe, T. Matsushita, K. Kaibuchi, and M. A. Schwartz. Integrin activation and matrix binding mediate cellular responses to mechanical stretch. J. Biol. Chem. 280:16546–16549, 2005.

    Article  Google Scholar 

  32. Kaunas, R., H. J. Hsu, and S. Deguchi. Sarcomeric model of stretch-induced stress fiber reorganization. Cell Health Cytoskeleton 3:13–22, 2011.

    Google Scholar 

  33. Kaunas, R., P. Nguyen, S. Usami, and S. Chien. Cooperative effects of Rho and mechanical stretch on stress fiber organization. Proc. Natl Acad. Sci. USA 102:15895–15900, 2005.

    Article  Google Scholar 

  34. Kaunas, R., S. Usami, and S. Chien. Regulation of stretch-induced JNK activation by stress fiber orientation. Cell. Signal. 18:1924–1931, 2006.

    Article  Google Scholar 

  35. Kawakami, K., H. Tatsumi, and M. Sokabe. Dynamics of integrin clustering at focal contacts of endothelial cells studied by multimode imaging microscopy. J. Cell Sci. 114:3125–3135, 2001.

    Google Scholar 

  36. Kumar, S., I. Z. Maxwell, A. Heisterkamp, T. R. Polte, T. P. Lele, M. Salanga, E. Mazur, and D. E. Ingber. 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.

    Article  Google Scholar 

  37. Kushida, N., Y. Kabuyama, O. Yamaguchi, and Y. Homma. Essential role for extracellular Ca(2+) in JNK activation by mechanical stretch in bladder smooth muscle cells. Am. J. Physiol. Cell Physiol. 281:C1165–C1172, 2001.

    Google Scholar 

  38. Langanger, G., M. Moeremans, G. Daneels, A. Sobieszek, M. De Brabander, and J. De Mey. The molecular organization of myosin in stress fibers of cultured cells. J. Cell Biol. 102:200–209, 1986.

    Article  Google Scholar 

  39. Lazarides, E., and K. Burridge. Alpha-actinin: immunofluorescent localization of a muscle structural protein in nonmuscle cells. Cell 6:289–298, 1975.

    Article  Google Scholar 

  40. Lee, C. F., C. Haase, S. Deguchi, and R. Kaunas. Cyclic stretch-induced stress fiber dynamics—dependence on strain rate, Rho-kinase and MLCK. Biochem. Biophys. Res. Commun. 401:344–349, 2010.

    Google Scholar 

  41. Lu, L., Y. Feng, W. J. Hucker, S. J. Oswald, G. D. Longmore, and F. C. Yin. Actin stress fiber pre-extension in human aortic endothelial cells. Cell Motil. Cytoskeleton 65:281–294, 2008.

    Article  Google Scholar 

  42. Maciver, S. K., H. G. Zot, and T. D. Pollard. Characterization of actin filament severing by actophorin from Acanthamoeba castellanii. J. Cell Biol. 115:1611–1620, 1991.

    Article  Google Scholar 

  43. MacKenna, D. A., F. Dolfi, K. Vuori, and E. Ruoslahti. Extracellular signal-regulated kinase and c-Jun NH2-terminal kinase activation by mechanical stretch is integrin-dependent and matrix-specific in rat cardiac fibroblasts. J. Clin. Invest. 101:301–310, 1998.

    Article  Google Scholar 

  44. Matsui, T. S., K. Ito, R. Kaunas, M. Sato, and S. Deguchi. Actin stress fibers are at a tipping point between conventional shortening and rapid disassembly at physiological levels of MgATP. Biochem. Biophys. Res. Commun. 395:301–306, 2010.

    Article  Google Scholar 

  45. Mizutani, T., H. Haga, and K. Kawabata. Cellular stiffness response to external deformation: tensional homeostasis in a single fibroblast. Cell Motil. Cytoskeleton 59:242–248, 2004.

    Article  Google Scholar 

  46. Neidlinger-Wilke, C., E. S. Grood, J.-C. Wang, R. A. Brand, and L. Claes. Cell alignment is induced by cyclic changes in cell length: studies of cells grown in cyclically stretched substrates. J. Orthop. Res. 19:286–293, 2001.

    Article  Google Scholar 

  47. Park, J. S., J. S. Chu, C. Cheng, F. Chen, D. Chen, and S. Li. Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells. Biotechnol. Bioeng. 88:359–368, 2004.

    Article  Google Scholar 

  48. Polte, T. R., G. S. Eichler, N. Wang, and D. E. Ingber. Extracellular matrix controls myosin light chain phosphorylation and cell contractility through modulation of cell shape and cytoskeletal prestress. Am. J. Physiol. Cell Physiol. 286:C518–C528, 2004.

    Article  Google Scholar 

  49. Ridley, A. J., and A. Hall. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389–399, 1992.

    Article  Google Scholar 

  50. Riveline, D., E. Zamir, N. Q. Balaban, U. S. Schwarz, T. Ishizaki, S. Narumiya, Z. Kam, B. Geiger, and A. D. Bershadsky. Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol. 153:1175–1186, 2001.

    Article  Google Scholar 

  51. Russell, R. J., S. L. Xia, R. B. Dickinson, and T. P. Lele. Sarcomere mechanics in capillary endothelial cells. Biophys. J. 97:1578–1585, 2009.

    Article  Google Scholar 

  52. Sanger, J. W., J. M. Sanger, and B. M. Jockusch. Differences in the stress fibers between fibroblasts and epithelial cells. J. Cell Biol. 96:961–969, 1983.

    Article  Google Scholar 

  53. Sato, K., T. Adachi, M. Matsuo, and Y. Tomita. Quantitative evaluation of threshold fiber strain that induces reorganization of cytoskeletal actin fiber structure in osteoblastic cells. J. Biomech. 38:1895–1901, 2005.

    Article  Google Scholar 

  54. Sato, K., T. Adachi, Y. Shirai, and N. Saito. Local disassembly of actin stress fibers induced by selected release of intracellular tension in osteoblastic cells. J. Biomech. Sci. Eng. 1:204–214, 2006.

    Article  Google Scholar 

  55. Sawada, Y., and M. P. Sheetz. Force transduction by Triton cytoskeletons. J. Cell Biol. 156:609–615, 2002.

    Article  Google Scholar 

  56. Sawada, Y., M. Tamada, B. J. Dubin-Thaler, O. Cherniavskaya, R. Sakai, S. Tanaka, and M. P. Sheetz. Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell 127:1015–1026, 2006.

    Article  Google Scholar 

  57. Schoenwaelder, S. M., and K. Burridge. Bidirectional signaling between the cytoskeleton and integrins. Curr. Opin. Cell Biol. 11:274–286, 1999.

    Article  Google Scholar 

  58. Simpson, D. G., M. Majeski, T. K. Borg, and L. Terracio. Regulation of cardiac myocyte protein turnover and myofibrillar structure in vitro by specific directions of stretch. Circ. Res. 85:e59–e69, 1999.

    Google Scholar 

  59. Smith, M. A., E. Blankman, M. L. Gardel, L. Luettjohann, C. M. Waterman, and M. C. Beckerle. A zyxin-mediated mechanism for actin stress fiber maintenance and repair. Dev. Cell 19:365–376, 2010.

    Article  Google Scholar 

  60. Smith, P. G., C. Roy, Y. N. Zhang, and S. Chauduri. Mechanical stress increases RhoA activation in airway smooth muscle cells. Am. J. Respir. Cell Mol. Biol. 28:436–442, 2003.

    Article  Google Scholar 

  61. Stachowiak, M. R., and B. O’Shaughnessy. Recoil after severing reveals stress fiber contraction mechanisms. Biophys. J. 97:462–471, 2009.

    Article  Google Scholar 

  62. Stamenovic, D., K. A. Lazopoulos, A. Pirentis, and B. Suki. Mechanical stability determines stress fiber and focal adhesion orientation. Cell. Mol. Bioeng. 2:475–485, 2009.

    Article  Google Scholar 

  63. Takei, T., C. Rivas-Gotz, C. A. Delling, J. T. Koo, I. Mills, T. L. McCarthy, M. Centrella, and B. E. Sumpio. Effect of strain on human keratinocytes in vitro. J. Cell. Physiol. 173:64–72, 1997.

    Article  Google Scholar 

  64. Takemasa, T., T. Yamaguchi, Y. Yamamoto, K. Sugimoto, and K. Yamashita. Oblique alignment of stress fibers in cells reduces the mechanical stress in cyclically deforming fields. Eur. J. Cell Biol. 77:91–99, 1998.

    Google Scholar 

  65. Tanner, K., A. Boudreau, M. J. Bissell, and S. Kumar. Dissecting regional variations in stress fiber mechanics in living cells with laser nanosurgery. Biophys. J. 99:2775–2783, 2010.

    Article  Google Scholar 

  66. Totsukawa, G., Y. Yamakita, S. Yamashiro, D. J. Hartshorne, Y. Sasaki, and F. Matsumura. Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. J. Cell Biol. 150:797–806, 2000.

    Article  Google Scholar 

  67. Wang, J. H. Substrate deformation determines actin cytoskeleton reorganization: a mathematical modeling and experimental study. J. Theor. Biol. 202:33–41, 2000.

    Article  Google Scholar 

  68. Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat. Cell Biol. 1:136–143, 1999.

    Article  Google Scholar 

  69. Wei, Z., V. S. Deshpande, R. M. McMeeking, and A. G. Evans. Analysis and interpretation of stress fiber organization in cells subject to cyclic stretch. J. Biomech. Eng. 130:031009, 2008.

    Google Scholar 

  70. Wilson, C. A., M. A. Tsuchida, G. M. Allen, E. L. Barnhart, K. T. Applegate, P. T. Yam, L. Ji, K. Keren, G. Danuser, and J. A. Theriot. Myosin II contributes to cell-scale actin network treadmilling through network disassembly. Nature 465:373–377, 2010.

    Article  Google Scholar 

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

    Article  Google Scholar 

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Acknowledgments

The authors were supported by grants from the American Heart Association (0730238N) and the National Science Foundation (CBET-0854129) to RK and by Special Coordination Funds for Promoting Science and Technology and Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (#21680039) to SD.

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  1. Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843-3120, USA

    Roland Kaunas

  2. Department of Biomedical Engineering, Tohoku University, Sendai, Japan

    Shinji Deguchi

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Correspondence to Roland Kaunas.

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Associate Editors Yingxiao Wang & Peter J. Butler oversaw the review of this article.

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Kaunas, R., Deguchi, S. Multiple Roles for Myosin II in Tensional Homeostasis Under Mechanical Loading. Cel. Mol. Bioeng. 4, 182–191 (2011). https://doi.org/10.1007/s12195-011-0175-x

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