A bio-chemo-mechanical model for cell contractility

A general model for the contractility of cells is presented that accounts for the dynamic reorganization of the cytoskeleton. The model is motivated by three key biochemical processes: (i) an activation signal that triggers actin polymerization and myosin phosphorylation, (ii) the tension-dependent assembly of the actin and myosin into stress fibers, and (iii) the cross-bridge cycling between the actin and myosin filaments that generates the tension. Simple relations are proposed to model these coupled phenomena and a continuum model developed for simulating cell contractility. The model is capable of predicting key experimentally established characteristics including: (i) the decrease in the forces generated by the cell with increasing substrate compliance, (ii) the influence of cell shape and boundary conditions on the development of structural anisotropy, and (iii) the high concentration of the stress fibers at the focal adhesions. We present numerical examples of a square cell on four supports to demonstrate these capabilities.

[1]  Christopher S. Chen,et al.  Cells lying on a bed of microneedles: An approach to isolate mechanical force , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Gregory M. Fomovsky,et al.  The development of structural and mechanical anisotropy in fibroblast populated collagen gels. , 2005, Journal of biomechanical engineering.

[3]  Frederick Grinnell,et al.  Fibroblasts, myofibroblasts, and wound contraction , 1994, The Journal of cell biology.

[4]  C F Dewey,et al.  Theoretical estimates of mechanical properties of the endothelial cell cytoskeleton. , 1996, Biophysical journal.

[5]  Daniel Choquet,et al.  Extracellular Matrix Rigidity Causes Strengthening of Integrin–Cytoskeleton Linkages , 1997, Cell.

[6]  Ning Wang,et al.  Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  Joachim P Spatz,et al.  A theoretical description of elastic pillar substrates in biophysical experiments. , 2005, Chemphyschem : a European journal of chemical physics and physical chemistry.

[8]  K. Burridge,et al.  Focal adhesions, contractility, and signaling. , 1996, Annual review of cell and developmental biology.

[9]  D. Ingber.  Mechanosensation through integrins: Cells act locally but think globally , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  F. Grinnell,et al.  Stress relaxation of contracted collagen gels: disruption of actin filament bundles, release of cell surface fibronectin, and down-regulation of DNA and protein synthesis. , 1991, Experimental cell research.

[11]  P. Janmey,et al.  Nonlinear elasticity in biological gels , 2004, Nature.

[12]  R. Franke,et al.  Induction of human vascular endothelial stress fibres by fluid shear stress , 1984, Nature.

[13]  Alexander A Spector,et al.  Emergent patterns of growth controlled by multicellular form and mechanics. , 2005, Proceedings of the National Academy of Sciences of the United States of America.