Department of Physics, University of Colorado, Boulder, Colorado.
Department of Physics, University of Colorado, Boulder, Colorado.
Biophys J. 2019 May 7;116(9):1719-1731. doi: 10.1016/j.bpj.2019.03.013. Epub 2019 Apr 13.
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.
细胞通过大规模细胞骨架重组来生长、移动和对外界刺激做出反应。细胞骨架重塑的一个典型例子是有丝分裂纺锤体的组装，在此过程中微管核生成、经历动态不稳定性、束集并组织成双极纺锤体。该过程的关键机制包括调节丝状聚合、交联和马达蛋白活性。值得注意的是，使用被动交联剂，裂殖酵母可以在没有马达蛋白的情况下组装双极纺锤体。我们开发了一种扭矩平衡模型来描述由于动态微管束、纺锤体极体、核膜和被动交联剂的存在而导致的这种重排，以预测纺锤体组装动力学。我们将这些结果与包含交联结合动力学和其他随机效应的动力学蒙特卡罗-布朗动力学模拟的结果进行了比较。我们的结果表明，快速的交联剂到微管重叠的重排促进了交联剂驱动的纺锤体组装，这是对未来实验的一个可测试的预测。结合这两种建模技术，我们说明了研究细胞骨架网络重排的一般方法。
