Geometrical and mechanical properties control actin filament organization

PLoS Comput Biol. 2015 May 27;11(5):e1004245. doi: 10.1371/journal.pcbi.1004245. eCollection 2015 May.

Abstract

The different actin structures governing eukaryotic cell shape and movement are not only determined by the properties of the actin filaments and associated proteins, but also by geometrical constraints. We recently demonstrated that limiting nucleation to specific regions was sufficient to obtain actin networks with different organization. To further investigate how spatially constrained actin nucleation determines the emergent actin organization, we performed detailed simulations of the actin filament system using Cytosim. We first calibrated the steric interaction between filaments, by matching, in simulations and experiments, the bundled actin organization observed with a rectangular bar of nucleating factor. We then studied the overall organization of actin filaments generated by more complex pattern geometries used experimentally. We found that the fraction of parallel versus antiparallel bundles is determined by the mechanical properties of actin filament or bundles and the efficiency of nucleation. Thus nucleation geometry, actin filaments local interactions, bundle rigidity, and nucleation efficiency are the key parameters controlling the emergent actin architecture. We finally simulated more complex nucleation patterns and performed the corresponding experiments to confirm the predictive capabilities of the model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry*
  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • Biomechanical Phenomena
  • Computational Biology
  • Computer Simulation
  • Humans
  • In Vitro Techniques
  • Models, Molecular*
  • Protein Multimerization*

Grants and funding

This work was funded by Agence Nationale de la Recherche Grants ANR-12-BSV5-0014-02; the European Commission Seventh Framework Programme (FP7/2007–2013) under grant agreements no. 241548 and 258068; Labex Grenoble Alliance for Integrated Structural Cell Biology; and CTBU Grant from CEA to Gaëlle Letort. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.