Mechanisms of Contractility and Coarsening of Active Cytoskeletal Networks

Abstract

Rapid structural remodeling of the cytoskeleton underlies many crucial processes such as cell polarization, division, and migration. Active remodeling involves the production and dissipation of forces within networks of actin filaments, molecular motors, and passive cross-linkers. However, despite its central importance, the underlying mechanisms remain unclear. A key challenge is to understand how global patterns of force buildup and dissipation during structural remodeling depend on the intrinsic properties of individual cytoskeletal components and their local interactions. To address this challenge, we have developed a three-dimensional agent-based computational model of a cross-linked actomyosin network with minimal components: actin filaments, passive cross-linkers, and active bipolar motors. Our model accounts for several key features neglected by previous studies, despite their likely significance for network remodeling including: volume-exclusion effects, the bending and thermal fluctuation of actin filaments, and the force-dependent unbinding and walking behaviors of the motors. Using the model, we systematically studied the influences of interplay between motors, cross-linkers, and actin dynamics on the contractility and structural dynamics of actomyosin networks. We found three different regimes determined by interplay between the sensitivity of motor unbinding to force and the stall-force level where motors cease walking: i) maximum tension and minimum deformation at low unbinding sensitivity, ii) intermediate tension and maximum deformation at intermediate sensitivity, iii) minimum tension and intermediate deformation at high sensitivity. We show further that passive cross-linkers can effectively tune networks between these regimes by maintaining percolation as well as by precluding large deformation of networks. Towards identifying mechanisms for rapid turnover of contractile foci, as observed in living cells, we are systematically investigating the effects of actin dynamics - assembly, disassembly, severing, capping, and aging - on the active contractile behaviors.