The dynamics of filament assembly define cytoskeletal network morphology

Abstract

The actin cytoskeleton is a key component in the machinery of eukaryotic cells, and it self-assembles out of equilibrium into a wide variety of biologically crucial structures. Although the molecular mechanisms involved are well characterized, the physical principles governing the spatial arrangement of actin filaments are not understood. Here we propose that the dynamics of actin network assembly from growing filaments results from a competition between diffusion, bundling and steric hindrance, and is responsible for the range of observed morphologies. Our model and simulations thus predict an abrupt dynamical transition between homogeneous and strongly bundled networks as a function of the actin polymerization rate. This suggests that cells may effect dramatic changes to their internal architecture through minute modifications of their nonequilibrium dynamics. Our results are consistent with available experimental data.

Nonequilibrium phase diagrams for actomyosin networks

“…For this reason, we restrict our attention to actin concentrations at which we expect the network connectivity to dominate the dynamics. This precludes modeling active nematic systems 34,35 , previously studied by others 36–38 ; it may also lead to quantitative artifacts in the rates of structure formation (owing to a lack of entanglement 39 ) and in density-dependent statistics of states with features such as contracted clusters or bundles. Overall, however, the model yields results in good agreement with observations for many cases of experimental interest 16,31 .…”

“…It would be straightforward to modify the energy function of the model to introduce geometric restrictions, and studies of passive systems indicate that such terms can introduce additional structural phases 26 . The model can also be extended to include actin polymerization and turnover, which have been shown to modulate contractility 42,61 and bundling 39 . Finally, the model can be parameterized for other polymer assemblies, such as microtubules, kinesin, and dynein, which form vortices and polarity sorted asters 29,62,63 .…”

Event-Chain Monte-Carlo Simulations of Dense Soft Matter Systems

“…Further numerical progress requires a faster equilibration of dense bundle structures. Simulations of larger systems consisting of cytoskeletal filaments and crosslinkers [63][64][65] show different competing phases from isotropic networks to bundles and other aggregates, for example, with bond-orientational order. In Ref.…”

“…In Ref. [65], it was also pointed out that the dynamics of bundling and polymerization in combination with entanglement of polymers strongly influence the resulting structure. This raises the question to what extent bundled structures can reach a genuine equilibrium under realistic conditions.…”

Molecular simulations of cellular processes

“…Simulating macromolecule stability and interactions in a eukaryotic-like cell requires a large effort for the presence of localized and pervasive structures (Neri et al 2013;Smith et al 2014;Unterberger and Holzapfel 2014;Mak et al 2015Mak et al , 2016Gao et al 2015;Nguyen et al 2016;Popov et al 2016;Reddy and Sansom 2016;Chavent et al 2016;Foffano et al 2016;Niesen et al 2017;Tachikawa and Mochizuki 2017). Future investigations will be devoted to simulating dynamical processes involving the cytoskeleton and the membranes, such as the trafficking of macromolecules and vesicles to their sub-cellular localization (Miller et al 2016).…”