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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DOI：
10.1371/journal.pcbi.1004877
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发表时间：
2016-04-01
影响因子：
4.3
通讯作者：
Papoian, Garegin A.
中科院分区：
文献类型：
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作者：
Popov, Konstantin;Komianos, James;Papoian, Garegin A.
活性物质系统，特别是细胞骨架，表现出复杂的机械化学动力学，仍然没有很好地理解。虽然细胞骨架动力学的先前计算模型已经导致了许多概念性的见解，但是仍然需要用高分辨率结构建模框架来填充一个重要的利基，该框架包括细胞骨架化学的最小完整集合，stochemistry在三个空间维度中处理反应和扩散过程，准确且有效地描述丝状网络在分子马达产生的应力下的机械变形，并以高空间分辨率将力学和化学深度耦合。为了满足这一需求，我们提出了一种新的反应粗粒度力场，以及一个公开可用的软件包，名为主动网络的机械化学动力学（MEDYAN），用于模拟主动网络的演变和动态（可在www.medyan.org）。该模型可用于研究活性物质系统中的非线性、远离平衡的过程，特别是由嵌入具有复杂反应扩散过程的溶液中的相互作用的半柔性聚合物组成的活性物质系统。在这项工作中，我们应用MEDYAN研究了由肌动蛋白丝、α-辅肌动蛋白交联蛋白和非肌肉肌球蛋白IIA迷你丝组成的收缩性肌动球蛋白网络。我们发现，这些系统经历了一个开关式的过渡，在模拟从一个随机的网络，有序的，捆绑的结构时，交联剂的浓度增加到阈值以上，诱导收缩肌球蛋白II微丝驱动。我们的模拟还显示了如何肌球蛋白II微丝，在串联与交联剂，可以产生一系列的肌动蛋白丝极性分布和对齐，这是至关重要的依赖于肌动蛋白丝的周转率和肌动蛋白丝的超扩散行为中的肌动球蛋白交联剂系统。我们讨论了这些研究结果的生物学意义的弧形成在板状体到板状体的建筑重塑。最后，我们的模拟产生肌球蛋白II的力依赖性积累，这被认为是负责其机械感觉能力，也自发地产生肌球蛋白II浓度梯度的模拟体积的溶液相。
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 nonmuscle myosin IIA mini-filaments. We found that these systems undergo a switch-like transition in simulations froma 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.