Simulated actin reorganization mediated by motor proteins

PLoS Comput Biol. 2022 Apr 7;18(4):e1010026. doi: 10.1371/journal.pcbi.1010026. eCollection 2022 Apr.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actins* / metabolism
  • Cytoskeleton / metabolism
  • Dyneins
  • Kinesins
  • Kinetics
  • Myosins* / metabolism

Substances

  • Actins
  • Myosins
  • Dyneins
  • Kinesins

Grants and funding

M.-V.C. has been supported by The Ohio State University President’s Postdoctoral Scholars Program and by the Mathematical Biosciences Institute at The Ohio State University through the National Science Foundation (NSF) DMS-1440386 (https://www.nsf.gov/div/index.jsp?div=DMS). A.T.D. is supported by the National Science Foundation (NSF) under Grant DMS-1554896 (https://www.nsf.gov/div/index.jsp?div=DMS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.