Actin reorganization throughout the cell cycle mediated by motor proteins

TL;DR

This study uses stochastic simulations to explore how different myosin motor proteins influence actin network organization during the cell cycle, revealing mechanisms of motor cooperation, antagonism, and regulation.

Contribution

It introduces a novel agent-based modeling framework and data analysis methods to study actin-myosin interactions and organization dynamics in silico.

Findings

Motor parameters like binding rate and step size affect actin contractility.

Different motor populations can cooperate or compete to organize actin networks.

Parameter regimes can lead to spatial segregation of motor types.

Abstract

Cortical actin networks are highly dynamic and play critical roles in shaping the mechanical properties of cells. The actin cytoskeleton undergoes significant reorganization over the course of the cell cycle, when cortical actin transitions between 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 model simulations 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. 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.