MEDYAN: Mechanochemical Simulations of Contraction and Polarity Alignment in Actomyosin Networks
MEDYAN: Mechanochemical Simulations of Contraction and Polarity Alignment in Actomyosin Networks
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Date
2016
Authors
Popov, Konstantin
Komianos, James
Papoian, Garegin A.
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PLoS Computational Biology
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Abstract
Active matter systems, and in particular the cell cytoskeleton, exhibit complex mechanochemical
dynamics that are still not well understood. While prior computational models of
cytoskeletal dynamics have lead to many conceptual insights, an important niche still
needs to be filled with a high-resolution structural modeling framework, which includes
a minimally-complete set of cytoskeletal chemistries, stochastically treats reaction and
diffusion processes in three spatial dimensions, accurately and efficiently describes mechanical
deformations of the filamentous network under stresses generated by molecular
motors, and deeply couples mechanics and chemistry at high spatial resolution. To
address this need, we propose a novel reactive coarse-grained force field, as well as a
publicly available software package, named the Mechanochemical Dynamics of Active
Networks (MEDYAN) , for simulating active network evolution and dynamics (available at
www.medyan.org). This model can be used to study the non-linear, far from equilibrium
processes in active matter systems, in particular, comprised of interacting semi-flexible
polymers embedded in a solution with complex reaction-diffusion processes. In this work,
we applied MEDYAN to investigate a contractile actomyosin network consisting of actin
filaments, alpha-actinin cross-linking proteins, and non-muscle myosin IIA mini-filaments.
We found that these systems undergo a switch-like transition in simulations from a random
network to ordered, bundled structures when cross-linker concentration is increased
above a threshold value, inducing contraction driven by myosin II mini-filaments. Our
simulations also show how myosin II mini-filaments, in tandem with cross-linkers, can
produce a range of actin filament polarity distributions and alignment, which is crucially
dependent on the rate of actin filament turnover and the actin filament's resulting
super-diffusive behavior in the actomyosin-cross-linker system. We discuss the biological
implications of these findings for the arc formation in lamellipodium-to-lamellum architectural
remodeling. Lastly, our simulations produce force-dependent accumulation of
myosin II, which is thought to be responsible for their mechanosensation ability, also
spontaneously generating myosin II concentration gradients in the solution phase of the
simulation volume.