Theory of Cytoskeletal Reorganization during Cross-Linker-Mediated Mitotic Spindle Assembly
Theory of Cytoskeletal Reorganization during Cross-Linker-Mediated Mitotic Spindle Assembly
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DOI：
10.1016/j.bpj.2019.03.013
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发表时间：
2019-05-07
影响因子：
3.4
通讯作者：
Betterton, Meredith D.
中科院分区：
文献类型：
--
作者：
Lamson, Adam R.;Edelmaier, Christopher J.;Betterton, Meredith D.
细胞生长、运动，并通过大规模的细胞骨架重组对外界刺激作出反应。细胞骨架重塑的典型例子是有丝分裂纺锤体组装，在此期间微管成核，经历动态不稳定性，捆绑并组织成双极纺锤体。这一过程的关键机制包括调控的纤维聚合、交联和运动蛋白活性。值得注意的是，使用被动交联剂，分裂酵母可以在没有马达蛋白的情况下组装双极纺锤体。我们开发了一个扭矩平衡模型，描述了这种重组，因为动态微管束，纺锤体，核被膜，和被动交联剂来预测纺锤体组装动力学。我们将这些结果与动力学蒙特卡罗-布朗动力学模拟，其中包括交联剂结合动力学和其他随机效应。我们的研究结果表明，快速的交联剂重组微管重叠促进交联剂驱动的纺锤体组装，可测试的预测未来的实验。结合这两种建模技术，我们说明了一个一般的方法来研究细胞骨架网络重组。
Cells grow, move, and respond to outside stimuli by large-scale cytoskeletal reorganization. A prototypical example of cytoskeletal remodeling is mitotic spindle assembly, during which microtubules nucleate, undergo dynamic instability, bundle, and organize into a bipolar spindle. Key mechanisms of this process include regulated filament polymerization, cross-linking, and motor-protein activity. Remarkably, using passive cross-linkers, fission yeast can assemble a bipolar spindle in the absence of motor proteins. We develop a torque-balance model that describes this reorganization because of dynamic microtubule bundles, spindle-pole bodies, the nuclear envelope, and passive cross-linkers to predict spindle-assembly dynamics. We compare these results to those obtained with kinetic Monte Carlo-Brownian dynamics simulations, which include cross-linker-binding kinetics and other stochastic effects. Our results show that rapid cross-linker reorganization to microtubule overlaps facilitates cross-linker-driven spindle assembly, a testable prediction for future experiments. Combining these two modeling techniques, we illustrate a general method for studying cytoskeletal network reorganization.