Modeling and Simulation of Myosin-Dependent Rearrangement and Force Generation in an Actomyosin Network

Abstract

Non-muscle myosin II and actin constitute the major force-generating machinery of actomyosin networks, whose contractility is essential for processes that require cellular reshaping and movement such as cell migration and cell division. In particular, mechanical behaviors of actomyosin networks such as spontaneous rearrangements of networks into bundles are recognized as being fundamental to biological functions but the mechanochemical basis of the emergence of these functions is still unclear. Thus, to clarify the mechanochemical foundation of the emergence of cellular functions, understanding the relationship between actomyosin contractility and rearrangement of actomyosin networks is crucial. For this purpose, we present a new particulate-based model for simulating the motions of actin, non-muscle myosin II, and alpha-actinin. To confirm the model's validity, we successfully simulated sliding and bending motions of actomyosin filaments, which are observed as fundamental behaviors in dynamic rearrangement of actomyosin networks in migrating keratocytes. Next, we simulated the dynamic rearrangement of actomyosin networks. Our simulation results indicate that an increase in the density fraction of myosin induces a higher-order structural transition of actomyosin filaments from networks to bundles, in addition to increasing the force generated by actomyosin filaments in the network. We compare our simulation results with experimental results and confirm that actomyosin bundles bridging focal adhesions and the characteristics of myosin-dependent rearrangement of actomyosin networks agree qualitatively with those observed experimentally.