Modeling myosin Va liposome transport through actin filament networks reveals a percolation threshold that modulates transport properties.
Modeling myosin Va liposome transport through actin filament networks reveals a percolation threshold that modulates transport properties.
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DOI：
10.1091/mbc.e21-08-0389
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发表时间：
2022-02-01
影响因子：
3.3
通讯作者：
Warshaw, D. M.
中科院分区：
文献类型：
--
作者：
Walcott, S.;Warshaw, D. M.
肌球蛋白Va（myoVa）马达通过三维细胞内肌动蛋白丝网络运输膜结合的货物。我们开发了一个粗粒度的计算机模型来预测随机取向的肌动蛋白网络内的肌动蛋白丝密度（3-800丝）如何影响myoVa马达的流体样脂质体（350 nm与1750 nm）运输。在每个网络中运输的5000个模拟脂质体采用三种状态之一：运输、拔河或扩散。由于脂质体从肌动蛋白分离的扩散很少发生，脂质体表面上至少有10个电机。然而，随着肌动蛋白密度的增加，脂质体从主要针对单个肌动蛋白丝的运输转变为明显的随机行走，这是由于运输和拔河的混合物，因为遇到额外的肌动蛋白丝的概率增加。这种相变是由临界数量的肌动蛋白丝Nc处的渗流相变引起的。Nc是肌动蛋白网络的几何性质，其仅取决于肌动蛋白丝的位置和极性、运输距离和脂质体直径，如脂质体直径增加五倍导致Nc减少五倍所证明的。因此，在细胞中，肌动蛋白网络密度和货物的大小可以进行调节，以匹配货物交付细胞的生理需求。
Myosin Va (myoVa) motors transport membrane-bound cargo through three-dimensional, intracellular actin filament networks. We developed a coarse-grained, in silico model to predict how actin filament density (3-800 filaments) within a randomly oriented actin network affects fluid-like liposome (350 nm vs. 1750 nm) transport by myoVa motors. Five thousand simulated liposomes transported within each network adopted one of three states: transport, tug-of-war, or diffusion. Diffusion due to liposome detachment from actin rarely occurred given at least 10 motors on the liposome surface. However, with increased actin density, liposomes transitioned from primarily directed transport on single actin filaments to an apparent random walk, resulting from a mixture of transport and tug-of-wars as the probability of encountering additional actin filaments increased. This phase transition arises from a percolation phase transition at a critical number of accessible actin filaments, Nc. Nc is a geometric property of the actin network that depends only on the position and polarity of the actin filaments, transport distance, and the liposome diameter, as evidenced by a fivefold increase in liposome diameter resulting in a fivefold decrease in Nc. Thus in cells, actin network density and cargo size may be regulated to match cargo delivery to the cell’s physiological demands.