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Introduction, with the biological basis for cell mechanics


state can exert a force on their surroundings. Forces have been measured in resting fibroblasts, for example, where intracellular tension gives rise to stresses in the focal adhesions of the cell adherent to a flexible two-dimensional substrate of about 5 nN/µm2, or 5 kPa (Balaban, Schwarz et al., 2001). In experiments with various cell types grown in a three-dimensional gel such as collagen, the cells actively contract the matrix by more than 50 percent (Sieminski, Hebbel et al., 2004). These contractile forces are associated with intracellular molecular motors such as those in the myosin family.


This book presents a full spectrum of views on current approaches to modeling cell mechanics. In part, this diversity of opinion stems from the different backgrounds of contributors to the field. Indeed, the authors of this book come from the biophysics, bioengineering, and physical chemistry communities, and each joins the discussion with a unique perspective on biological systems. Consequently, the approaches range from finite element methods commonly used in continuum mechanics to models of the cytoskeleton as a cross-linked polymer network to models of soft glassy materials and gels. Studies reflect both the static, instantaneous nature of the structure as well as its dynamic nature due to polymerization and the full array of biological processes. It is unlikely that a single unifying approach will evolve from this diversity, in part because of the complexity of the phenomena underlying the mechanical properties of the cell. It is our hope, however, that a better appreciation of the various perspectives will lead to a more highly coordinated approach to the essential problems and might facilitate discussions among investigators with differing views.

Perhaps the most important purpose of this monograph is to stimulate new ideas and approaches. Because no single method has emerged as clearly superior, this might reflect the need for approaches not yet envisaged. That much of the work presented here derives from publications over the past several years reinforces the notion that cell mechanics is a rapidly evolving field. The next decade will likely yield further advances not yet foreseen.


Balaban, N. Q., U. S. Schwarz, et al. (2001). “Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates.” Nat. Cell Biol., 3(5): 466–72.

Bao, G. and S. Suresh (2003). “Cell and molecular mechanics of biological materials.” Nat. Mater., 2(11): 715–25.

Bindschadler M., O. E., Dewey C. F. Jr, McGrath, J. L. (2004). “A mechanistic model of the actin cycle.” Biophys. J., 86: 2720–2739.

Chang, G., R. H. Spencer, et al. (1998). “Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel.” Science, 282(5397): 2220–6.

Chen, C. S., J. Tan, et al. (2004). “Mechanotransduction at cell-matrix and cell-cell contacts.” Annu. Rev. Biomed. Eng., 6: 275–302.

Christopher, R. A. and J. L. Guan (2000). “To move or not: how a cell responds (Review).” Int. J. Mol. Med., 5(6): 575–81.

Dahl, K. N., A. J. Engler, et al. (2005). “Power-law rheology of isolated nuclei with deformation mapping of nuclear substructures.” Biophys. J., 89(4): 2855–64.

16R. D. Kamm and M. R. K. Mofrad

Dahl, K. N., S. M. Kahn, et al. (2004). “The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber.” J. Cell Sci., 117(Pt 20): 4779–86.

Davies, P. F. (1995). “Flow-mediated endothelial mechanotransduction.” Physiol. Rev., 75(3): 519– 60.

Davies, P. F. (2002). “Multiple signaling pathways in flow-mediated endothelial mechanotransduction: PYK-ing the right location.” Arterioscler Thromb Vasc. Biol., 22(11): 1755–7.

Dewey, C. F., Jr., S. R. Bussolari, et al. (1981). “The dynamic response of vascular endothelial cells to fluid shear stress.” J. Biomech. Eng., 103(3): 177–85.

DiMilla, P. A., K. Barbee, et al. (1991). “Mathematical model for the effects of adhesion and mechanics on cell migration speed.” Biophys. J., 60(1): 15–37.

Evans, E. and W. Rawicz (1990). “Entropy-driven tension and bending elasticity in condensed-fluid membranes.” Phys. Rev. Lett., 64(17): 2094–2097.

Friedl, P., Y. Hegerfeldt, et al. (2004). “Collective cell migration in morphogenesis and cancer.” Int. J. Dev. Biol., 48(5-6): 441–9.

Geiger, B. and A. Bershadsky (2002). “Exploring the neighborhood: adhesion-coupled cell mechanosensors.” Cell, 110(2): 139–42.

Gimbrone, M. A., Jr., J. N. Topper, et al. (2000). “Endothelial dysfunction, hemodynamic forces, and atherogenesis.” Ann. N Y Acad. Sci., 902: 230-9; discussion 239–40.

Gittes, F., B. Mickey, et al. (1993). “Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape.” J. Cell Biol., 120(4): 923–34.

Gullingsrud, J., D. Kosztin, et al. (2001). “Structural determinants of MscL gating studied by molecular dynamics simulations.” Biophys. J., 80(5): 2074–81.

Hamill, O. P. and B. Martinac (2001). “Molecular basis of mechanotransduction in living cells.” Physiol. Rev., 81(2): 685–740.

Helmke, B. P., D. B. Thakker, et al. (2001). “Spatiotemporal analysis of flow-induced intermediate filament displacement in living endothelial cells.” Biophys. J., 80(1): 184–94.

Higuchi, H. and Y. E. Goldman (1995). “Sliding distance per ATP molecule hydrolyzed by myosin heads during isotonic shortening of skinned muscle fibers.” Biophys. J., 69(4): 1491–507.

Horwitz, R. and D. Webb (2003). “Cell migration.” Curr. Biol., 13(19): R756–9.

Howard, J., (2001) Mechanics of Motor Proteins and the Cytoskeleton, Sinauer Associates, Inc., pp. 288–289.

Huang, H., R. D. Kamm, et al. (2004). “Cell mechanics and mechanotransduction: pathways, probes, and physiology.” Am. J. Physiol. Cell Physiol., 287(1): C1–11.

Hudspeth, A. J. (2001). “How the ear’s works work: mechanoelectrical transduction and amplification by hair cells of the internal ear.” Harvey Lect., 97: 41–54.

Hudspeth, A. J., Y. Choe, et al. (2000). “Putting ion channels to work: mechanoelectrical transduction, adaptation, and amplification by hair cells.” Proc. Natl. Acad. Sci. USA, 97(22): 11765–72.

Ingber, D. E. (1998). “Cellular basis of mechanotransduction.” Biol. Bull., 194(3): 323–5; discussion 325–7.

Janmey, P. A. and D. A. Weitz (2004). “Dealing with mechanics: mechanisms of force transduction in cells.” Trends Biochem. Sci., 29(7): 364–70.

Lehoux, S. and A. Tedgui (2003). “Cellular mechanics and gene expression in blood vessels.” J. Biomech., 36(5): 631–43.

Malek, A. M. and S. Izumo (1994). “Molecular aspects of signal transduction of shear stress in the endothelial cell.” J. Hypertens., 12(9): 989–99.

McCormick, S. M., S. R. Frye, et al. (2003). “Microarray analysis of shear stressed endothelial cells.” Biorheology, 40(1–3): 5–11.

Mitchison, T. and M. Kirschner (1984). “Dynamic instability of microtubule growth.” Nature, 312(5991): 237–42.

Mohandas, N. and E. Evans (1994). “Mechanical properties of the red cell membrane in relation to molecular structure and genetic defects.” Annu. Rev. Biophys. Biomol. Struct., 23: 787–818.

Mucke, N., L. Kreplak, et al. (2004). “Assessing the flexibility of intermediate filaments by atomic force microscopy.” J. Mol. Biol., 335(5): 1241–50.

Introduction, with the biological basis for cell mechanics


Scheffer, L., A. Bitler, et al. (2001). “Atomic force pulling: probing the local elasticity of the cell membrane.” Eur. Biophys. J., 30(2): 83–90.

Shyy, J. Y. and S. Chien (2002). “Role of integrins in endothelial mechanosensing of shear stress.” Circ. Res., 91(9): 769–75.

Sieminski, A. L., R. P. Hebbel, et al. (2004). “The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro.” Exp. Cell Res., 297(2): 574–84.

Singer, S. J. and G. L. Nicolson (1972). “The fluid mosaic model of the structure of cell membranes.” Science, 175(23): 720–31.

Strey, H., M. Peterson, et al. (1995). “Measurement of erythrocyte membrane elasticity by flicker eigenmode decomposition.” Biophys. J., 69(2): 478–88.

Tseng, Y., K. M. An, et al. (2004). “The bimodal role of filamin in controlling the architecture and mechanics of F-actin networks.” J. Biol. Chem., 279(3): 1819–26.

Tsuda, Y., H. Yasutake, et al. (1996). “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(23): 12937–42.

Waugh, R. and E. A. Evans (1979). “Thermoelasticity of red blood cell membrane.” Biophys. J., 26(1): 115–31.

Yasuda, R., H. Miyata, et al. (1996). “Direct measurement of the torsional rigidity of single actin filaments.” J. Mol. Biol., 263(2): 227–36.

Zhelev, D. V., D. Needham, et al. (1994). “Role of the membrane cortex in neutrophil deformation in small pipets.” Biophys. J., 67(2): 696–705.