Geometrical and Mechanical Properties Control Actin Filament Organization

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.

Architecture and Connectivity Govern Actin Network Contractility

“…To understand how different actin architectures respond to myosin-induced contraction, we performed detailed simulations of the different types of actin rings—disordered network, disordered and ordered bundles using Cytosim (Figures 2A and S2A; Movie S4; [30, 31]). We implemented our simulation with entities mimicking molecular motors with properties similar to myosin VI (Figures 2A and S2B).…”

A Combination of Actin Treadmilling and Cross-Linking Drives Contraction of Random Actomyosin Arrays

“…The velocities of actin and myosin are determined by the force balance equations. Following many previous models (7,18,27,29), we consider a balance of two types of forces: active myosin and passive cross-linking forces (30). Actomyosin interactions are specified by coefficients w ik{ 0,1} (1 if the ith filament is bound to the kth cluster, zero otherwise).…”

“…where F s is the myosin stall force (30). Effective drag force due to the cross linking originates from protein friction that stems from continuous turnover, attachment, detachment, and stretching of elastic cross-linking proteins.…”

Density fields for branching, stiff networks in rigid confining regions

“…Therefore the variation of z 0 and ζ 0 allows us to obtain different types of confined networks and the numerical results show distinct differences between the spatial density distribution of filament segment profiles of these networks. Imaging of actin cytoskeletal networks inside living cells using electron and fluorescence microscopy has shown highly ordered dense structure in the vicinity of the cell membrane [14,24,15,41,42,43]. Indeed many studies have been conducted to investigate the origin of the ordering of these networks.…”