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What are the Cellular Responses to Mechanotransduction?


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Essential Info: What are the Cellular Responses to Mechanotransduction?

3.1 Introduction

Mechanotransduction is an iterative process, involving multiple rounds of mechano-sensing, -transduction, and -response. It is a means by which force-induced conformational and/or biochemical changes result in the activation and amplification of intracellular signaling cascades. These cascades lead to a cellular response i.e. mechanoresponse, which feeds back into the loop of mechanotransduction. Consequently, a highly dynamic steady state can be reached through repeated cycles of force-sensing and concomitant cellular remodeling (reviewed in [1]). The cellular mechanoresponse often takes the form of a change in morphology and/or motility, which is facilitated by the generation of force by the cell itself.

Cell shape remodeling and cell locomotion specifically require the cell to produce two types of force; a protruding force to extend the leading edge forward and traction forces to move the cell body [1] (reviewed in [2, 3]). Although this seems relatively simple, a number of factors contribute to generating the forces needed for modifying cell shape and for cell motility, including:
  • Forces produced by nucleotide binding, controlled hydrolysis, and release of inorganic phosphate
    Energy from nucleotide hydrolysis is used to promote actin filament elongation [4], to promote the translocation of motor proteins along cytoskeletal filaments (reviewed in [5]) and is stored within cytoskeletal lattices to generate a resting tension within the cell [6].
  • Forces produced by filament self-assembly
    Cytoskeletal filament self-assembly generates thermodynamic driving forces [7, 8, 9, 10] (reviewed in [11, 12]) for mechanical restructuring of the cell shape [13] and for driving cell motility [14, 15, 16]. Both polymer dynamics and their concentration can be directly modified by force, which serves as an inherent feedback system (reviewed by [17]).
  • Forces produced by higher-order structuring of the filaments
    Cytoskeletal filaments generate tensional forces and exert traction forces on their adhesions to the extracellular matrix (ECM) or to other cells, thereby generating a resting tension within the cell (reviewed in [18, 19]).
The generation of force, whether at the level of single molecules or macromolecular filament structures, allows the cell to exert changes in response to specific mechanical stimuli. These changes are both varied and highly specific and include:
  • cell polarity
  • cellular adhesion [20, 21]
  • direction of cell movement [22, 23, 24]
  • cell fate [14, 25, 26, 27]
  • cell shape [13, 28]
  • production of ECM components [29]
  • patterns of tissue growth [30]

References

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  2. Ingber DE. Tensegrity II. How structural networks influence cellular information processing networks. J. Cell. Sci. 2003; 116(Pt 8):1397-408. [PMID: 12640025]
  3. Dalby MJ., Riehle MO., Sutherland DS., Agheli H. & Curtis AS. Morphological and microarray analysis of human fibroblasts cultured on nanocolumns produced by colloidal lithography. Eur Cell Mater 2005; 9:1-8; discussion 8. [PMID: 15690263]
  4. Dickinson RB., Caro L. & Purich DL. Force generation by cytoskeletal filament end-tracking proteins. Biophys. J. 2004; 87(4):2838-54. [PMID: 15454475]
  5. Hwang W. & Lang MJ. Mechanical design of translocating motor proteins. Cell Biochem. Biophys. 2009; 54(1-3):11-22. [PMID: 19452133]
  6. Ingber DE. Tensegrity I. Cell structure and hierarchical systems biology. J. Cell. Sci. 2003; 116(Pt 7):1157-73. [PMID: 12615960]
  7. Hill TL. Microfilament or microtubule assembly or disassembly against a force. Proc. Natl. Acad. Sci. U.S.A. 1981; 78(9):5613-7. [PMID: 6946498]
  8. Peskin CS., Odell GM. & Oster GF. Cellular motions and thermal fluctuations: the Brownian ratchet. Biophys. J. 1993; 65(1):316-24. [PMID: 8369439]
  9. Peskin CS. & Oster GF. Force production by depolymerizing microtubules: load-velocity curves and run-pause statistics. Biophys. J. 1995; 69(6):2268-76. [PMID: 8599634]
  10. Dogterom M. & Yurke B. Measurement of the force-velocity relation for growing microtubules. Science 1997; 278(5339):856-60. [PMID: 9346483]
  11. Theriot JA. The polymerization motor. Traffic 2000; 1(1):19-28. [PMID: 11208055]
  12. Howard J. & Hyman AA. Dynamics and mechanics of the microtubule plus end. Nature 2003; 422(6933):753-8. [PMID: 12700769]
  13. Keren K., Pincus Z., Allen GM., Barnhart EL., Marriott G., Mogilner A. & Theriot JA. Mechanism of shape determination in motile cells. Nature 2008; 453(7194):475-80. [PMID: 18497816]
  14. Mogilner A. & Oster G. Cell motility driven by actin polymerization. Biophys. J. 1996; 71(6):3030-45. [PMID: 8968574]
  15. Loisel TP., Boujemaa R., Pantaloni D. & Carlier MF. Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Nature 1999; 401(6753):613-6. [PMID: 10524632]
  16. Footer MJ., Kerssemakers JW., Theriot JA. & Dogterom M. Direct measurement of force generation by actin filament polymerization using an optical trap. Proc. Natl. Acad. Sci. U.S.A. 2007; 104(7):2181-6. [PMID: 17277076]
  17. Khan S. & Sheetz MP. Force effects on biochemical kinetics. Annu. Rev. Biochem. 1997; 66:785-805. [PMID: 9242924]
  18. Ingber DE. Tensegrity-based mechanosensing from macro to micro. Prog. Biophys. Mol. Biol.; 97(2-3):163-79. [PMID: 18406455]
  19. Ingber DE. Tensegrity: the architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 1997; 59:575-99. [PMID: 9074778]
  20. Giannone G., Dubin-Thaler BJ., Rossier O., Cai Y., Chaga O., Jiang G., Beaver W., Döbereiner HG., Freund Y., Borisy G. & Sheetz MP. Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell 2007; 128(3):561-75. [PMID: 17289574]
  21. Geiger B., Spatz JP. & Bershadsky AD. Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell Biol. 2009; 10(1):21-33. [PMID: 19197329]
  22. Jiang X., Bruzewicz DA., Wong AP., Piel M. & Whitesides GM. Directing cell migration with asymmetric micropatterns. Proc. Natl. Acad. Sci. U.S.A. 2005; 102(4):975-8. [PMID: 15653772]
  23. Yam PT., Wilson CA., Ji L., Hebert B., Barnhart EL., Dye NA., Wiseman PW., Danuser G. & Theriot JA. Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J. Cell Biol. 2007; 178(7):1207-21. [PMID: 17893245]
  24. Brock A., Chang E., Ho CC., LeDuc P., Jiang X., Whitesides GM. & Ingber DE. Geometric determinants of directional cell motility revealed using microcontact printing. Langmuir 2003; 19(5):1611-7. [PMID: 14674434]
  25. McBeath R., Pirone DM., Nelson CM., Bhadriraju K. & Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 2004; 6(4):483-95. [PMID: 15068789]
  26. Ingber DE. & Folkman J. Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. J. Cell Biol. 1989; 109(1):317-30. [PMID: 2473081]
  27. Griffin MA., Sen S., Sweeney HL. & Discher DE. Adhesion-contractile balance in myocyte differentiation. J. Cell. Sci. 2004; 117(Pt 24):5855-63. [PMID: 15522893]
  28. Chen CS., Ostuni E., Whitesides GM. & Ingber DE. Using self-assembled monolayers to pattern ECM proteins and cells on substrates. Methods Mol. Biol. 2000; 139:209-19. [PMID: 10840789]
  29. Lee CH., Shin HJ., Cho IH., Kang YM., Kim IA., Park KD. & Shin JW. Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast. Biomaterials 2005; 26(11):1261-70. [PMID: 15475056]
  30. Nelson CM., Jean RP., Tan JL., Liu WF., Sniadecki NJ., Spector AA. & Chen CS. Emergent patterns of growth controlled by multicellular form and mechanics. Proc. Natl. Acad. Sci. U.S.A. 2005; 102(33):11594-9. [PMID: 16049098]
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Sruthi Jagannathan,
Nov 6, 2012, 11:32 PM