Shanghai Key Laboratory for Contemporary Applied Mathematics, Centre for Computational Systems Biology, School of Mathematical Sciences, Fudan University, Shanghai 200433, China.
J Biol Chem. 2011 Nov 11;286(45):39439-49. doi: 10.1074/jbc.M111.260208. Epub 2011 Sep 7.
In this study, a two-state mechanochemical model is presented to describe the dynamic instability of microtubules (MTs) in cells. The MT switches between two states, the assembly and disassembly states. In assembly state, the growth of MTs includes two processes: free GTP-tubulin binding to the tip of protofilament (PF) and conformation change of PF, during which the first tubulin unit that curls outwards is rearranged onto the MT surface, using the energy released from the hydrolysis of GTP in the penultimate tubulin unit. In the disassembly state, the shortening of MTs also includes two processes, the release of GDP-tubulin from the tip of PF and the curling of one new tubulin unit out of the MT surface. Switches between these two states, which are usually called rescue and catastrophe, happen stochastically with external force-dependent rates. Using this two-state model with parameters obtained by fitting the recent experimental data, detailed properties of MT growth are obtained. I find that MT is mainly in the assembly state, its mean growth velocity increases with both the external force and the GTP-tubulin concentration, and an MT will shorten on average without an external force. To know more about the external force and GTP-tubulin concentration-dependent properties of MT growth, and for future experimental verification of this two-state model, 11 critical forces are defined and discussed numerically.
在这项研究中，提出了一个两态机械化学模型来描述细胞中微管（MT）的动态不稳定性。MT 在两种状态之间切换，即组装和拆卸状态。在组装状态下，MT 的生长包括两个过程：游离 GTP-微管蛋白结合到原纤维（PF）的尖端和 PF 的构象变化，在此过程中，向外卷曲的第一个微管蛋白单元被重新排列到 MT 表面上，利用来自倒数第二个微管蛋白单元中 GTP 水解释放的能量。在拆卸状态下，MT 的缩短也包括两个过程，即 GDP-微管蛋白从 PF 尖端的释放和一个新的微管蛋白单元从 MT 表面卷曲出来。这些两种状态之间的转换，通常称为救援和灾难，以与外力相关的随机速率发生。使用这个具有通过拟合最近的实验数据获得的参数的两态模型，获得了 MT 生长的详细性质。我发现 MT 主要处于组装状态，其平均生长速度随外力和 GTP-微管蛋白浓度的增加而增加，并且在没有外力的情况下 MT 平均会缩短。为了更好地了解 MT 生长对外部力和 GTP-微管蛋白浓度的依赖性，以及为了未来对这个两态模型的实验验证，我们定义并数值讨论了 11 个临界力。
