有丝分裂中微管寻找和捕获染色体的首次通过时间理论
A first-passage-time theory for search and capture of chromosomes by microtubules in mitosis
摘要：
有丝分裂纺锤体是真核细胞细胞分裂的重要中间结构，其中一对复制染色体中的每一个都通过微管附着在靠近分裂细胞两极的中心体上。纺锤体的形成有几种机制，其中之一是通过随机搜索微管“捕获”由动粒结合在一起的染色体对。虽然整个细胞周期可以长达24小时，但有丝分裂期通常只需不到一小时。细胞是如何将有丝分裂的持续时间保持在这个限度内的？先前的理论研究表明，染色体的搜索和捕获是通过调整微管动力学参数，以最小化搜索时间来优化的。在本文中，我们研究这个猜想。我们计算的平均搜索时间为一个单一的目标微管从一个单一的成核网站，使用系统和严格的理论方法，为任意的动力学参数。通过物理论证，将结果推广到多靶和多形核位置。然后使用实验数据获得不同细胞的有丝分裂时间尺度的估计。在酵母和哺乳动物细胞中，所观察到的微管动力学在间期和有丝分裂之间的变化有利于减少搜索时间。相反，在{ \it爪蟾}提取物中，观察到相反的效果，这与目前的理解一致，即大细胞使用额外的机制来调节有丝分裂期的持续时间。
英文摘要：
The mitotic spindle is an important intermediate structure in eukaryotic cell division, in which each of a pair of duplicated chromosomes is attached through microtubules to centrosomal bodies located close to the two poles of the dividing cell. Several mechanisms are at work towards the formation of the spindle, one of which is the `capture' of chromosome pairs, held together by kinetochores, by randomly searching microtubules. Although the entire cell cycle can be up to 24 hours long, the mitotic phase typically takes only less than an hour. How does the cell keep the duration of mitosis within this limit? Previous theoretical studies have suggested that the chromosome search and capture is optimized by tuning the microtubule dynamic parameters to minimize the search time. In this paper, we examine this conjecture. We compute the mean search time for a single target by microtubules from a single nucleating site, using a systematic and rigorous theoretical approach, for arbitrary kinetic parameters. The result is extended to multiple targets and nucleating sites by physical arguments. Estimates of mitotic time scales are then obtained for different cells using experimental data. In yeast and mammalian cells, the observed changes in microtubule kinetics between interphase and mitosis are beneficial in reducing the search time. In {\it Xenopus} extracts, by contrast, the opposite effect is observed, in agreement with the current understanding that large cells use additional mechanisms to regulate the duration of the mitotic phase.
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