Simulated actin reorganization mediated by motor proteins

摘要

Author summaryCell shape is dictated by a scaffolding network called the cytoskeleton. Actin filaments, a main component of the cytoskeleton, are found predominantly at the periphery of the cell, where they organize into different patterns in response to various stimuli, such as progression through the cell cycle. The actin filament reorganizations are mediated by motor proteins from the myosin superfamily. Using a realistic stochastic model that simulates actin filament and motor protein dynamics and interactions, we systematically vary motor protein kinetics and investigate their effect on actin filament organization. Using novel measures of spatial organization, we quantify conditions under which motor proteins, either alone or in combination, can produce the different actin filament organizations observed in vitro and in vivo. These results yield new insights into the role of motor proteins, as well as into how multiple types of motors can work collectively to produce specific actomyosin network patterns. Cortical actin networks are highly dynamic and play critical roles in shaping the mechanical properties of cells. The actin cytoskeleton undergoes significant reorganization in many different contexts, including during directed cell migration and over the course of the cell cycle, when cortical actin can transition between different configurations such as open patched meshworks, homogeneous distributions, and aligned bundles. Several types of myosin motor proteins, characterized by different kinetic parameters, have been involved in this reorganization of actin filaments. Given the limitations in studying the interactions of actin with myosin in vivo, we propose stochastic agent-based models and develop a set of data analysis measures to assess how myosin motor proteins mediate various actin organizations. In particular, we identify individual motor parameters, such as motor binding rate and step size, that generate actin networks with different levels of contractility and different patterns of myosin motor localization, which have previously been observed experimentally. In simulations where two motor populations with distinct kinetic parameters interact with the same actin network, we find that motors may act in a complementary way, by tuning the actin network organization, or in an antagonistic way, where one motor emerges as dominant. This modeling and data analysis framework also uncovers parameter regimes where spatial segregation between motor populations is achieved. By allowing for changes in kinetic rates during the actin-myosin dynamic simulations, our work suggests that certain actin-myosin organizations may require additional regulation beyond mediation by motor proteins in order to reconfigure the cytoskeleton network on experimentally-observed timescales.