Department of Physics, Indian Institute of Technology Kanpur, 208016, India.
Phys Biol. 2014 Jun;11(3):036004. doi: 10.1088/1478-3975/11/3/036004. Epub 2014 Apr 24.
Before a cell divides into two daughter cells, chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes, thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an in vitro experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed 'catch-bond-like' behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the in vitro experiments, provided that the experiment is repeated a sufficiently large number of times. Our theory provides a deep insight into the effects of (a) size, (b) energetics, and (c) stochastic kinetics of the kt-MT coupling on the distribution of the lifetimes of these attachments.
在细胞分裂为两个子细胞之前，染色体被复制，形成两个相互拥抱的姐妹染色体。每个姐妹染色体都与一个称为动粒（kinetochore，kt）的独立蛋白结构结合，该结构可以捕获丝状蛋白微管（microtubule，MT）的末端。两个相反方向的 MT 拉动附着在两个姐妹染色体上的两个 kt，从而将两个姐妹彼此拉开。在这里，我们从理论上研究了一个更简单的系统，即与单个 MT 相连的孤立 kt；该系统模拟了使用从芽殖酵母中纯化的提取物重新构建单个 kt-MT 附着的体外实验。我们的模型不仅解释了实验中观察到的 kt-MT 偶联的“类捕获键”行为，还对附着的寿命的概率分布做出了新的预测。原则上，如果在体外实验中重复足够多次，可以通过分析收集的数据来检验我们的新预测。我们的理论深入了解了 kt-MT 偶联的（a）大小、（b）能量学和（c）随机动力学对这些附着的寿命分布的影响。
