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12 - Protein Conformational Change

A Molecular Basis of Mechanotransduction

Published online by Cambridge University Press:  05 July 2014

By
Gang Bao
Edited by
Mohammad R. K. Mofrad  and
Roger D. Kamm
Gang Bao
Affiliation:
Emory University
Mohammad R. K. Mofrad
Affiliation:
University of California, Berkeley
Roger D. Kamm
Affiliation:
Massachusetts Institute of Technology
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Summary

Cells Can Sense and Respond to Mechanical Forces

The biological cell constitutes the basic unit of life and performs a large variety of functions through synthesis, sorting, storage, and transport of biomolecules; expression of genetic information; recognition, transmission, and transduction of signals; and converting different forms of energy [1]. Many of the cellular processes involve mechanical force, or deformation, at the cellular, subcellular, and molecular levels [2, 3]. For example, biomolecular motors and machines convert chemical energy into mechanical motion in performing their diverse range of functions [4, 5]. During cell migration, contractile forces must be generated within the cell in order for the cell body to move forward [6]. Adhesion of cells to an extracellular matrix (ECM) through focal adhesion complexes is sensitive to the stiffness of the substrate [7, 8]. All living cells on Earth are constantly under physical force (gravitational and other forms of force), and many normal and diseased conditions of cells are dependent on or regulated by their mechanical environment. Some cells, such as bone and endothelial cells, are subjected to specific forces as part of their “native” physiological environment. Some other cells, such as muscle and cochlear outer hair cells [9], perform a mechanical function by converting an electrical or chemical stimulus into a mechanical motion.

Type
Chapter
Information
Cellular Mechanotransduction
Diverse Perspectives from Molecules to Tissues
 , pp. 269 - 285
Publisher: Cambridge University Press
Print publication year: 2009

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References

Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K., Watson, J. D. (2002) Molecular Biology of the Cell. 4th ed. Garland Publishing, New York.Google Scholar
Wang, N., Butler, J. P., Ingber, D. E. (1993) Mechanotransduction across the cell surface and through the cytoskeleton. Science, 260, 1124–1127.CrossRefGoogle ScholarPubMed
Vogel, V., Sheetz, M. (2006) Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol, 7, 265–275.CrossRefGoogle ScholarPubMed
Howard, J. (2001) Mechanics of Motor Proteins and the Cytoskeleton. Sinauer Associates, Sunderland, MA.Google Scholar
Block, S. M., Goldstein, L. S., et al. (1990) Bead movement by single kinesin molecules studied with optical tweezers. Nature, 348, 348–352.CrossRefGoogle ScholarPubMed
Stossel, T. P. (1993) On the crawling of animal cells. Science, 260, 1086–1094.CrossRefGoogle ScholarPubMed
Pelham, R. J. J., Wang, Y. (1997) Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Natl. Acad. Sci. U.S.A., 94, 13661– 13665.CrossRefGoogle ScholarPubMed
Discher, D. E., Janmey, P., Wang, Y. (2005) Tissue cells feel and respond to the stiffness of their substrate. Science, 310, 1139–1143.CrossRefGoogle ScholarPubMed
Brownell, W. E., Spector, A. A., Raphael, R. M., Popel, A. S. (2001) Micro- and nanomechanics of the cochlear outer hair cell. Annu. Rev. Biomed. Eng., 3, 169–194.CrossRefGoogle ScholarPubMed
Bao, G. (2002) Mechanics of biomolecules. J. Mech. Phys. Solids, 50, 2237–2274.CrossRefGoogle Scholar
Zhu, C., Bao, G. Wang, N. (2000) Cell mechanics: Mechanical response, cell adhesion, and molecular deformation. Annu. Rev. Biomed. Eng., 2, 189–226.CrossRefGoogle ScholarPubMed
Bershadsky, A. D., Balaban, N. Q., Geiger, B. (2003) Adhesion-dependent cell mechanosensitivity. Annu. Rev. Cell Dev. Biol., 19, 677–695.CrossRefGoogle ScholarPubMed
Bershadsky, A., Kozlov, M., Geiger, B. (2006) Adhesion-mediated mechanosensitivity: A time to experiment, and a time to theorize. Curr. Opin. Cell Biol., 18, 472–481.CrossRefGoogle Scholar
Jalali, S., del Pozo, M. A., Chen, K., Miao, H., Li, Y., Schwartz, M. A., Shyy, J. Y., Chien, S. (2001) Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc. Natl. Acad. Sci. U.S.A., 98, 1042–1046.CrossRefGoogle ScholarPubMed
Fung, Y. C. (1990) Biomechanics: Motion, Flow, Stress, and Growth. Springer-Verlag, New York.CrossRefGoogle Scholar
Fung, Y. C. (1993) Biomechanics: Mechanical Properties of Living Tissues. 2nd ed. Springer-Verlag, New York.CrossRefGoogle Scholar
Engler, A. J., Sen, S., Sweeney, H. L., Discher, D. E. (2006) Matrix elasticity directs stem cell lineage specification. Cell, 126, 677–689.CrossRefGoogle ScholarPubMed
Ali, M. H., Schumacker, P. T. (2002) Endothelial responses to mechanical stress: Where is the mechanosensor?. Crit. Care Med., 30, S198–206.CrossRefGoogle ScholarPubMed
Wootton, D. M., Ku, D. N. (1999) Fluid mechanics of vascular systems, diseases, and thrombosis. Annu. Rev. Biomed. Eng., 1, 299–329.CrossRefGoogle ScholarPubMed
Fisher, A. B., Chien, S., Barakat, A. I., Nerem, R. M. (2001) Endothelial cellular response to altered shear stress. Am. J. Physiol. Lung. Cell. Mol. Physiol., 281, L529–533.CrossRefGoogle Scholar
Hu, H., Sachs, F. (1997) Stretch-activated ion channels in the heart. J. Mol. Cell Cardiol., 29, 1511–1523.CrossRefGoogle ScholarPubMed
Ingber, D. E. (2002) Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circ. Res., 91, 877–887.CrossRefGoogle ScholarPubMed
Creighton, T. E. (1993) Proteins. W. H. Freeman and Company, New York.Google Scholar
Bao, G., Suresh, S. (2003) Cell and molecular mechanics of biological materials. Nat. Mat., 2, 715–726.CrossRefGoogle ScholarPubMed
Voet, D., Voet, J. G. (1995) Biochemistry. 2nd ed. John Wiley & Sons, New York.Google Scholar
McCammon, J. A., Gelin, B. R., Karplus, M., Wolynes, P. G. (1976) The hinge-bending mode in lysozyme. Nature, 262, 325–326.CrossRefGoogle ScholarPubMed
Rief, M., Gautel, M., Oesterhelt, F., Fernandez, J. M., Gaub, H. (1997) Reversible unfolding of individual titin immunoglobulin domains by AFM. Science, 276, 1109–1112.CrossRefGoogle ScholarPubMed
Kellermayer, M. S. Z., Smith, S. B., Granzier, H. L., Bustamante, C. (1997) Folding-unfolding transitions in single titin molecules characterized with laser tweezers. Science 276, 1112–1116.CrossRefGoogle ScholarPubMed
Tskhovrebova, L., Trinnick, J., Sleep, J. A., Simmons, R. M. (1997) Elasticity and unfolding of single molecules of the giant muscle protein titin. Nature, 387, 308–312.CrossRefGoogle ScholarPubMed
Oberhauser, A. F., Marszalek, P. E., Erickson, H. P., Fernandez, J. M. (1998) The molecular elasticity of the extracellular matrix protein tenascin. Nature, 393, 181–185.Google ScholarPubMed
Krammer, A., Lu, H., Isralewitz, B., Schulten, K., Vogel, V. (1999) Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch. Proc. Natl. Acad. Sci. U.S.A., 96, 1351–1356.CrossRefGoogle ScholarPubMed
Ohashi, T., Kiehart, D. P., Ericson, H. (1999) Dynamics and elasticity of the fibronectin matrix in living cell culture visualized by fibronectin-green fluorescent protein. Proc. Natl. Acad. Sci. U.S.A., 96, 2153–2158.CrossRefGoogle ScholarPubMed
Craig, D., Krammer, A., Schulten, K., Vogel, V. (2001) Comparison of the early stages of forced unfolding for fibronectin type III modules. Proc. Natl. Acad. Sci. U.S.A., 98, 5590–5595.CrossRefGoogle ScholarPubMed
Vogel, V., Thomas, W. E., Craig, D. W., Krammer, A., Baneyx, G. (2001) Structural insights into the mechanical regulation of molecular recognition sites. Trends. Biotechnol, 19, 416–423.CrossRefGoogle ScholarPubMed
Puklin-Faucher, E., Gao, M., Schulten, K., Vogel, V. (2006) How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation. J. Cell. Biol., 175, 349–360.CrossRefGoogle ScholarPubMed
Ruggeri, Z. M. (2003) Von Willebrand factor. Curr Opin Hematol, 10, 142–149.CrossRefGoogle ScholarPubMed
Johnson, C. P., Tang, H. Y., Carag, C., Speicher, D. W., Discher, D. E. (2007) Forced unfolding of proteins within cells. Science, 317, 663–666.CrossRefGoogle ScholarPubMed
Soto, C. (2001) Protein misfolding and disease; protein refolding and therapy. FEBS Letters, 498, 204–207.CrossRefGoogle ScholarPubMed
Fung, Y. C. (1967) Elasticity of soft tissues in simply elaongation. Am. J. Physiol., 28, 1532–1544.Google Scholar
Marko, J. F., Siggia, E. D. (1995) Streching DNA. Macromolecules, 28, 8759–8770.CrossRefGoogle Scholar
Schwaiger, I., Schleicher, M., Noegel, A. A., Rief, M. (2005) The folding pathway of a fast-folding immunoglobulin domain revealed by single-molecule mechanical experiments. EMBO Rep., 6, 46–51.CrossRefGoogle ScholarPubMed
Subbiah, S. (1996) Protein Motions. Chapman & Hall, Austin, TX.Google Scholar
Coffey, W. (1985) In Evans, M.W. (ed.), Dynamical Processes in Condensed Matter, pp. 69–252. John Wiley & Sons, New York.Google Scholar
Uhlenbeck, G. E., Ornstein, L. S. (1930) On the theory of the Brownian motion. Phys. Rev., 36, 823–841.CrossRefGoogle Scholar
Boyer, P. D. (1993) The binding change mechanism for ATP synthase – Some probabilities and possibilities. Biochem. Biophys. Acta, 1140, 215–250.Google ScholarPubMed
Lauffenburger, D. A., Linderman, J. J. (1993) Receptors. Oxford University Press, New York.Google Scholar
Israelachvili, J. (1992) Intermolecular and Surface Forces. Academic Press, San Diego, CA.Google Scholar
Evans, E., Ritchie, K. (1997) Dynamic strength of molecular adhesion bonds. Biophys. J., 72, 1541–1555.CrossRefGoogle ScholarPubMed
Merkel, R., Nassoy, P., Leung, A., Ritchie, K., Evans, E. (1999) Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature, 397, 50–53.CrossRefGoogle ScholarPubMed
Sanchez-Mateos, P., Cabanas, C., Sanchez-Madrid, F. (1996) Regulation of integrin function. Semin. Cancer Biol., 7, 99–109.CrossRefGoogle ScholarPubMed
Baneyx, G., Baugh, L., Vogel, V. (2001) Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer. Proc. Natl. Acad. Sci. U.S.A., 98, 14464–14468.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed

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