Material viscosity and plasticity regulated adhesion and spreading of cells

Abstract

Accumulating evidence has shown that, in addition to rigidity, the viscous and plastic response of the extracellular matrix (ECM) also significantly affect the behavior and function of cells. However, the mechanisms behind such mechanosensitivity remain unclear. In this talk, I will present our recent effort on this front. Specifically, by examining the dynamics of motor clutches (i.e., focal adhesions) formed between the cell and a viscoelastic substrate, we showed that, for low ECM rigidity, maximum cell spreading is achieved at an optimal level of viscosity in which the substrate relaxation time falls between the timescale for clutch binding and its characteristic binding lifetime. That is, viscosity serves to stiffen soft substrates on a timescale faster than the clutch off-rate, which enhances cell-ECM adhesion and cell spreading. On the other hand, for substrates that are stiff, our model predicts that viscosity will not influence cell spreading, since the bound clutches are saturated by the elevated stiffness. The model was tested and validated using experimental measurements on three different material systems and explained the different observed effects of viscosity on each substrate. Besides viscosity, we also investigated the influence of mechanical plasticity induced by interfiber cross-link breakage (in fibrous ECMs) on the growth of focal adhesions (FAs). Interestingly, it was found that contractile cells break cross-links in soft fibrous matrices leading to recruitment of fibers, which increases the ligand density in the vicinity of cells. Consequently, plasticity of fibrous networks could lead to a departure from the well-known positive correlation between ECM stiffness and FA size, in agreement with recent experiments.