Computational Insights Into Cytoskeletal Rheology

Abstract

Cytoskeletal rheology is critical in the interaction of cells with their environment. It influences cell migration, mechanotransduction, and the ability of the cell to transmit externally applied forces. Models for cell mechanics have progressed considerably in recent years, and are now capable of simulating the effects of thermal fluctuations, cross-linking, and stresses generated by motor activity, all thought to be important determinants of cytoskeletal viscoelastic behavior. At the same time, model systems such as reconstituted actin gels have been used to gain insight into the factors that give rise to the unique cytoskeletal behavior. Of interest in this regard are: (i) the unique power-law rheology observed in the linear stress regime, (ii) nonlinear strain stiffening, (iii) fluidization that occurs above some critical level of stress, beyond which the modulus falls precipitously, and (iv) the role of prestress on cell stiffness. Here we present results from recent models that address each of these phenomena. We show through modeling that (i) thermal fluctuations of actin filaments are important only at low levels of prestress and small values of the ratio of persistence length to distance between cross-links, (ii) power-law rheology appears to emerge as a consequence of motor-induced prestress and cross-links, (iii) in the strain-stiffening regime, prestress is the primary determinant of network modulus, (iv) cross-link rupture rather than unfolding accounts for network remodeling and stress relaxation behavior, (v) motor activity generates prestress, but also has a strong influence on network morphology and the formation of stress fibers. [Support from the Sumsung Scholarship Program (to TYK) and the NIH (GM076689) is gratefully acknowledged.]