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Responses of Cells to Adhesion-Mediated Signals: A Universal Mechanism

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Mechanobiology of Cell-Cell and Cell-Matrix Interactions

Abstract

Cells are exposed to a plethora of signals that typically coerce them to function properly, but aberrant signaling can lead to pathological conditions. In the treatment of diseases and the rational design of functioning tissues, it is vital to understand and be able to manipulate these inputs. In the past, much of the interest has been on chemical signaling but recently, there has been an explosion of research into a diverse array of mechanical signals. Mechanical signals have been shown to influence cellular growth, survival, migration, and differentiation. Despite its obvious importance, relatively little is known about the mechanism of mechanosensing. In this chapter, we describe what is currently known about potential mechanosensing molecules and then describe a model by which a wide array of mechanical signals can be interpreted by a common mechanism. By understanding this mechanism, one may be able to develop new therapeutic interventions for devastating diseases such as cancer and break through critical barriers facing the field of tissue engineering. We expect the knowledge gained from the study of basic biology to greatly impact the treatment of many patients in the clinical setting in the coming years.

This chapter is part of Section I: Mechanisms of Cell Adhesion and Mechanotransduction

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References

  1. Wang N, Tytell JD, Ingber DE (2009) Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat. Rev. Mol. Cell Biol. 10:75–82.

    Article  Google Scholar 

  2. Bershadsky AD, Balaban NQ, Geiger B (2003) Adhesion-dependent cell mechanosenstivity. Annu. Rev. Cell Dev. Biol. 19:677–695.

    Article  Google Scholar 

  3. Wang JH-C, Thampatty BP (2006) An introductory review of cell mechanobiology. Biomech. Model. Mechanobiol. 5:1–16.

    Article  Google Scholar 

  4. Discher DE, Janmey P, Wang YL (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310:1139–1143.

    Article  Google Scholar 

  5. Mammoto A, Connor KM, Mammoto T, Yung CW, Huh D, Aderman CM, Mostoslavsky G, Smith LE, Ingber DE (2009) A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457:1103–1108.

    Article  Google Scholar 

  6. Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE (1997) Geometric control of cell life and death. Science 276(5317):1425–1428.

    Article  Google Scholar 

  7. Thomas CH, Collier JH, Sfeir CS, Healy KE (2002) Engineering gene expression and protein synthesis by modulating nuclear shape. Proc. Natl. Acad. Sci. U.S.A. 99:1972–1977.

    Article  Google Scholar 

  8. Curtis A, Wilkinson C (1997) Topographical control of cells. Biomaterials 18:1573–1583.

    Article  Google Scholar 

  9. Wang HB, Dembo M, Wang YL (2000) Substrate flexibility regulates growth and apoptosis of normal but not transformed cells. Am. J. Physiol. 279:C1345–C1350.

    Google Scholar 

  10. Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689.

    Article  Google Scholar 

  11. Carvalho RS, Schaffer JL, Gerstenfeld LC (1998) Osteoblasts induce osteopontin expression in response to attachment on fibronectin: demonstration of a common role for integrin receptors in the signal transduction processes of cell attachment and mechanical stimulation, J. Cell. Biochem. 70:376–390.

    Article  Google Scholar 

  12. Spiegelman BM, Ginty GA (1983) Fibronectin modulation of cell shape and lipogenic gene expression in 3T3-adipocytes. Cell 35:657–666.

    Article  Google Scholar 

  13. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6:483–495.

    Article  Google Scholar 

  14. Lo CM, Wang HB, Dembo M, Wang, YL (2000) Cell movement is guided by the rigidity of the substrates. Biophys. J. 79:144–152.

    Article  Google Scholar 

  15. Lee J, Ishihara A, Oxford G, Johnson B, Jacobson K (1999) Regulation of cell movement is mediated by stretch-activated calcium channels. Nature 400:382–386.

    Article  Google Scholar 

  16. Sigurdson W, Ruknudin A, Sachs F (1992) Calcium imaging of mechanically induced fluxes in tissue cultured chick heart: role of stretch activated ion channels. Am. J. Physiol. Heart Circ. Physiol. 262:H1110–H1115.

    Google Scholar 

  17. Munevar S, Wang YL, Dembo M (2004) Regulation of mechanical interaction between fibroblasts and the substratum by stretch activated Ca2+ entry. J. Cell Sci. 117:85–92.

    Article  Google Scholar 

  18. Geiger B, Spatz JP, Bershadsky AD (2009) Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell. Biol. 10:21–33.

    Article  Google Scholar 

  19. Carragher NO, Frame MC (2004) Focal adhesion and actin dynamics: a place where kinases and proteases meet to promote invasion. Trends Cell Biol. 14:24–249.

    Article  Google Scholar 

  20. Chen CS, Tan J, Tien J (2004) Mechanotransduction at cell-matrix and cell-cell contacts. Annu. Rev. Biomed. Eng. 6:275–302.

    Article  Google Scholar 

  21. Riveline D, Zamir E, Balaban NQ, Schwarz US, Ishizaki T, Narumiya S, Kam Z, Geiger B, Bershadsky AD (2001) 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.

    Article  Google Scholar 

  22. Wang N, Butler JP, Ingber DE (1993) Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–1127.

    Article  Google Scholar 

  23. Choquet D, Felsenfeld DP, Sheetz MP (1997) Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell 88:39–48.

    Article  Google Scholar 

  24. Katsumi A et al (2004) Integrins in mechanotransduction. J. Biol. Chem. 279:12001–12004.

    Article  Google Scholar 

  25. Garcia AJ, Huber F, Boettiger D (1998) Force required to break α5β1 integrin-fibronectin bonds in intact adherent cells is sensitive to integrin activation state. J. Biol. Chem. 273(18):10988–10993.

    Article  Google Scholar 

  26. Paszek MJ, Boettiger D, Weaver VM, Hammer DA (2009) Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate. PLoS Comput. Biol. 5:1–16.

    Article  MathSciNet  Google Scholar 

  27. Wang HB, Dembo M, Wang YL (2001) Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc. Natl. Acad. Sci. U.S.A. 98:11295–11300.

    Article  Google Scholar 

  28. Wang Y et al (2005) Visualizing the mechanical activation of Src. Nature 434:1040–1045.

    Article  Google Scholar 

  29. Johnson RP, Craig SW (1995) F-actin binding site masked by the intramolecular association of vinculin head and tail domains. Nature 373:261–264.

    Article  Google Scholar 

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

    Article  Google Scholar 

  31. Guo WH, Wang YL (2007) Retrograde fluxes of focal adhesion proteins in response to cell migration and mechanical signals. Mol. Biol. Cell 18:4519–4527.

    Article  Google Scholar 

  32. Meinhardt H (1999) Orientation of chemotactic cells and growth cones: models and mechanisms. J. Cell Sci. 112:2867–2874.

    Google Scholar 

  33. Rappel WJ, Thomas PJ, Levine H, Loomis WF (2002) Establishing direction during chemotaxis in eukaryotic cells. Biophys. J. 83:1361–1367.

    Article  Google Scholar 

  34. Postma M, Bosgraaf L, Loovers HM, Van Haastert PJM (2004) Chemotaxis: signalling modules join hands at front and tail. EMBO Rep. 5:35–40.

    Article  Google Scholar 

  35. Schwartz MA, Schaller MD, Ginsberg MH (1995) Integrins: emerging paradigms of signal transduction. Annu. Rev. Cell. Dev. Biol. 11:549–599.

    Article  Google Scholar 

  36. Zhong CL, Chrzanowska-Wodnicka M, Brown J, Shaub A, Belkin AM, Burridge K (1998) Rho-mediated contractility exposes a cryptic site in fibronectin and induces fibronectin matrix assembly. J. Cell Biol. 141:539–551.

    Article  Google Scholar 

  37. Baneyx G, Baugh L, Vogel V (2002) Fibronectin extension and unfolding within cell matrix fibrils controlled by cytoskeletal tension. Proc. Natl. Acad. Sci. U.S.A. 99:5139–5143.

    Article  Google Scholar 

  38. Wierzbicka-Patynowski I, Schwarzbauer JE (2003) The ins and outs of fibronectin matrix assembly. J. Cell Sci. 116:3269–3276.

    Article  Google Scholar 

  39. Saez A, Buguin A, Silberzan P, Ladoux B (2005) Is the mechanical activity of epithelial cells controlled by deformations or forces? Biophys. J. 89:L52–L54

    Article  Google Scholar 

  40. Pelham RJ Jr., Wang YL (1997) Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Natl. Acad. Sci. U.S.A. 94:13661–13665.

    Article  Google Scholar 

  41. Wang N, Ostuni E, Whitesides G, Ingber DE (2002) Micropatterning tractional forces in living cells. Cell Motil. Cytoskeleton 52:97–106.

    Article  Google Scholar 

  42. Reinhart-King CA, Dembo M, Hammer DA (2003) Endothelial cell traction forces on RGD-derivatized polyacrylamide substrata. Langmuir 19:1573–1579.

    Article  Google Scholar 

  43. Danen EHJ, Yamada KM (2001) Fibronectin, integrins, and growth control. J. Cell Physiol. 189:1–13.

    Article  Google Scholar 

  44. Schwartz MA (1997) Integrins, oncogenes, and anchorage independence. J. Cell Biol. 139:575–578.

    Article  Google Scholar 

  45. Paszek MJ, Weaver VM (2004) The tension mounts: mechanics meets morphogenesis and malignancy. J. Mammary Gland Biol. Neoplasia 9:325–342.

    Article  Google Scholar 

  46. Levental I, Georges PC, Janmey PA (2007) Soft biological materials and their impact on cell function. Soft Matter 3:299–306.

    Article  Google Scholar 

  47. Huang S, Ingber DE (2005) Cell tension, matrix mechanics, and cancer development. Cancer Cell 8:175–176.

    Article  Google Scholar 

  48. Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, Reinhart-King CA, Margulies SS, Dembo M, Boettiger D, Hammer DA, Weaver VM (2005) Tensional homeostasis and the malignant phenotype. Cancer Cell 8:241–254.

    Article  Google Scholar 

  49. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, Fong SF, Csiszar K, Giaccia A, Weninger W, Yamauchi M, Gasser DL, Weaver VM (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139:891–906.

    Article  Google Scholar 

  50. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, Carey VJ, Richardson AL, Weinberg RA (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–348.

    Article  Google Scholar 

  51. Guo WH, Frey MT, Burnham NA, Wang YL (2006) Substrate rigidity regulates the formation and maintenance of tissues. Biophys. J. 90:2213–2220.

    Article  Google Scholar 

  52. Smith AG (2001) Embryo-derived stem cells: of mice and men. Annu. Rev. Cell Dev. Biol. 17:435–462.

    Article  Google Scholar 

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Correspondence to Yu-Li Wang .

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Rape, A.D., Guo, WH., Wang, YL. (2011). Responses of Cells to Adhesion-Mediated Signals: A Universal Mechanism. In: Wagoner Johnson, A., Harley, B. (eds) Mechanobiology of Cell-Cell and Cell-Matrix Interactions. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8083-0_1

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  • DOI: https://doi.org/10.1007/978-1-4419-8083-0_1

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