论文标题

在肌动蛋白驱动的运输下的波形蛋白组织模型

Models of Vimentin Organization Under Actin-Driven Transport

论文作者

Park, Youngmin, Leduc, Cécile, Etienne-Manneville, Sandrine, Portet, Stéphanie

论文摘要

中间细丝形成了一个必不可少的结构网络,分布在整个细胞质中,并在细胞力学,细胞内组织和分子信号传导中起关键作用。网络的维护及其对细胞动态行为的适应性依赖于涉及细胞骨架串扰的几种机制,这些机制尚未完全理解。数学建模使我们能够比较几个生物学现实的情景,以帮助我们解释实验数据。在这项研究中,我们观察并模拟了通过诺科唑处理微管破坏后,在圆形微图案上播种的单神经胶质细胞中波形蛋白中间丝的动力学。在这些条件下,波形蛋白丝向细胞中心移动并积聚,然后最终到达稳态。在没有微管驱动的运输的情况下,波形蛋白网络的运动主要由肌动蛋白相关的机制驱动。为了建模这些实验发现,我们假设波形蛋白可能存在于两个状态,即移动和不动,并且以未知状态(恒定或非恒定)速率在状态之间进行切换。假定移动波形蛋白以恒定或非恒定速度的速度升级。我们使用这组假设介绍了几种生物学上现实的场景。对于每种情况,我们都使用差分进化来找到最佳参数集,从而产生与实验数据最匹配的解决方案,然后使用Akaike信息标准评估假设。这种建模方法使我们能够得出结论,我们的实验数据是通过空间依赖的中间细丝或依赖肌动蛋白依赖性转运的空间依赖速度来解释的。

Intermediate filaments form an essential structural network, spread throughout the cytoplasm and play a key role in cell mechanics, intracellular organization and molecular signaling. The maintenance of the network and its adaptation to the cell's dynamic behavior relies on several mechanisms implicating cytoskeletal crosstalk which are not fully understood. Mathematical modeling allows us to compare several biologically realistic scenarios to help us interpret experimental data. In this study, we observe and model the dynamics of the vimentin intermediate filaments in single glial cells seeded on circular micropatterns following microtubule disruption by nocodazole treatment. In these conditions, the vimentin filaments move towards the cell center and accumulate before eventually reaching a steady-state. In absence of microtubule-driven transport, the motion of the vimentin network is primarily driven by actin-related mechanisms. To model these experimental findings, we hypothesize that vimentin may exist in two states, mobile and immobile, and switches between the states at unknown (either constant or non-constant) rates. Mobile vimentin are assumed to advect with either constant or non-constant velocity. We introduce several biologically realistic scenarios using this set of assumptions. For each scenario, we use differential evolution to find the best parameter sets resulting in a solution that most closely matches the experimental data, then the assumptions are evaluated using the Akaike Information Criterion. This modeling approach allows us to conclude that our experimental data are best explained by a spatially dependent trapping of intermediate filaments or a spatially dependent speed of actin-dependent transport.

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