migration consists of several steps involving multiple mechanobiological signals and events starting with the leading edge protrusion, formation of new adhesion plaques at the front edge, followed by contraction of the cell and the release of adhesions at the rear (see Li et al., 2005 for a recent review). A host of mechanical and biochemical factors, namely extracellular matrix cues, chemoattractant concentration gradients, substrate rigidity, and other mechanical signals, influence these processes. Many unanswered questions remain in understanding the signaling molecules that play a key role in cell migration, and how they are regulated both in time and 3D space. It is largely unknown how a cell actively controls the traction force at a focal adhesion or how this force varies with time during the cell migration.

To understand the mechanobiology of the cell requires a multiscale/multiphysics view of how externally applied stresses or traction forces are transmitted through focal adhesion receptors and distributed throughout the cell, leading subsequently to conformational changes that occur in individual mechanosensing proteins that in turn lead to increased enzymatic activity or altered binding affinities. This presents both a challenge and an opportunity for further research into the intrinsically coupled mechanobiological phenomena that eventually determine the macroscopic behavior and function of the cell.

Because no one method has emerged as clearly superior in describing the mechanics and biology of the cell across all cell types and physical conditions, this might reflect the need for new approaches and ideas. We hope that this monograph has inspired new researchers with fresh ideas directed toward that goal. Perhaps the biggest question that still remains is whether it is at all possible to construct a single model that is universally applicable and can be used to describe all types of cell mechanical behavior.

References

Bursac P, Lenormand G, Fabry B, Oliver M, Weitz DA, Viasnoff V, Butler JP, Fredberg JJ. “Cytoskeletal remodelling and slow dynamics in the living cell.” Nat. Mater., 4(7):557–61, 2005.

Gardel ML, Shin JH, MacKintosh FC, Mahadevan L, Matsudaira PA, Weitz DA. “Scaling of F-actin network rheology to probe single filament elasticity and dynamics.” Phys. Rev. Lett., 93(18):188102, 2004.

Geiger B, Bershadsky A, Pankov R, Yamada KM. “Transmembrane crosstalk between the extracellular matrix–cytoskeleton crosstalk.” Nat. Rev. Mol. Cell Biol., 2(11): 793–805, 2001.

Haidekker MA, L’Heureux N, Frangos JA. “Fluid shear stress increases membrane fluidity in endothelial cells: a study with DCVJ fluorescence.” Am. J. Physiol. Heart Circ. Physiol., 278(4):H1401–6, 2000.

Hamill OP, Martinac C. “Molecular basis of mechanotransduction in living cells.” Physiol. Rev., 81: 685–740, 2001.

Kamm RD and Kaazempur-Mofrad MR. “On the molecular basis for mechanotransduction,” Mech. Chem. Biosystems, Vol. 1(3):201–210, 2004.

Li S, Guan JL, Chien S. “Biochemistry and biomechanics of cell motility.” Annu. Rev. Biomed. Eng., 7:105–50, 2005.

Maniotis AJ, Chen CS, Ingber DE. “Demonstration of mechanical connections between integrins, cytoskeletal filaments and nucleoplasm that stabilize nuclear structure.” Proc. Natl. Acad. Sci. USA, 94:849–54, 1997.

Marquez JP, Genin GM, Zahalak GI, Elson EL. “The relationship between cell and tissue strain in three-dimensional bio-artificial tissues.” Biophys. J., 88(2):778–89, 2005.

230M.R.K. Mofrad and R.D. Kamm

Odde DJ, Ma L, Briggs AH, DeMarco A, Kirschner MW. “Microtubule bending and breaking in living fibroblast cells.” J. Cell Sci., 112:3283–8, 1999.

Tseng Y, Lee J S, Kole, T P, Jiang, I, and Wirtz, D. “Micro-organization and visco-elasticity of the interphase nucleus revealed by particle nanotracking.” J. Cell Sci., 117, 2159–67, 2004.

Tschumperlin DJ, Dai G, Maly IV, Kikuchi T, Laiho LH, McVittie AK, Haley KJ, Lilly CM, So PT, Lauffenburger DA, Kamm RD, Drazen JM. “Mechanotransduction through growth-factor shedding into the extracellular space.” Nature, 429: 83–6, 2004.