Contractility and Dissipation in Active Actin Bundles and Networks

Abstract

Actomyosin machinery is a fundamental engine generating mechanical forces required for biological processes of non-muscle cells such as cell migration, cytokinesis, and morphogenesis. The net force generation is determined by the buildup and dissipation of forces in bundles and networks consisting of actin filaments, molecular motors, and passive cross-linkers. Although the molecular and physical properties of key elements in the actomyosin machinery have been characterized well, it still remains unclear how macroscopic force buildup and dissipation depend on the microscopic properties of individual cytoskeletal components and their local interactions.To bridge such a gap between macroscopic and microscopic scales, we have developed a three-dimensional computational model of actomyosin bundles and networks with minimal components: actin filaments, passive cross-linkers, and active motors. Our model accounts for several key features neglected by previous studies despite their significance for force generation. Especially, the motors comprise a backbone structure with numerous heads attached as myosin thick filaments and mini-filaments, and kinetics of the individual heads is governed by mechanochemical rates for faithfully capturing behaviors of myosin II heads.Using the model, we systematically studied how a net force in bundles and networks is determined via interplay between actin filaments, motors, and cross-linkers. We found the maximal force buildup is affected mainly by the total number and stall force of heads and how stably motors walk on actin filaments. We showed further that passive cross-linkers can help force buildup by increasing connectivity but can also act as dampers by dissipating the forces via reversible binding to actin filaments. We also investigated effects of the density, length, and dynamics of actin filaments on the net force generation.