Comparative studies of microtubule mechanics with two competing models suggest functional roles of alternative tubulin lateral interactions.

Comparative studies of microtubule mechanics with two competing models suggest functional roles of alternative tubulin lateral interactions.
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微管力学与两种竞争模型的比较研究表明替代微管蛋白横向相互作用的功能作用。

DOI:
10.1016/j.bpj.2012.05.003
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发表时间:
2012
影响因子:
3.4
通讯作者:
Xing,Jianhua
Xing,Jianhua
中科院分区:
生物学3区
文献类型:
--
作者:
Wu,Zhanghan;Nogales,Eva;Xing,Jianhua

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微管的动态组装和拆卸以及这些聚合物的机械性质对于许多关键的细胞过程是必不可少的。数学和计算建模,特别是耦合机械化学建模,为我们理解微管动力学做出了重大贡献。然而,关键的差异之间存在的实验观察和建模结果,需要解决进一步的进展之前,一个完整的模型可以。在体外研究中,在微管的生长端经常观察到长度从几百纳米到一微米的开片结构。现有的建模研究预测这些片结构是短的和罕见的微管拆卸的中间体,而不是组装过程的重要组成部分。原子力显微镜(AFM)的研究还揭示了有趣的阶梯状缺口的力压痕曲线,还不能解释现有的理论模型。我们已经进行了计算研究,以比较两种替代模型的机械性能:一个更传统的模型,微管蛋白二聚体直接加入到微管晶格中,和一个认为额外类型的微管蛋白横向相互作用提出存在于中间片结构在微管组装过程中。第一个模型涉及一个单一类型的微管蛋白亚基之间的横向相互作用,而后者认为第二种类型,可以转换为典型的横向接触过程中微管关闭成一个圆柱体。我们的分析表明,只有第二个模型可以重现AFM的结果在一个广泛的参数范围。我们提出了额外的研究,使用不同大小的AFM提示,将允许明确区分两种模型的相对有效性。
The dynamic assembly and disassembly of microtubules and the mechanical properties of these polymers are essential for many key cellular processes. Mathematical and computational modeling, especially coupled mechanochemical modeling, has contributed significantly to our understanding of microtubule dynamics. However, critical discrepancies exist between experimental observations and modeling results that need to be resolved before further progress toward a complete model can be made. Open sheet structures ranging in length from several hundred nanometers to one micron have often been observed at the growing ends of microtubules in in vitro studies. Existing modeling studies predict these sheet structures to be short and rare intermediates of microtubule disassembly rather than important components of the assembly process. Atomic force microscopy (AFM) studies also reveal interesting step-like gaps of the force-indentation curve that cannot yet be explained by existing theoretical models. We have carried out computational studies to compare the mechanical properties of two alternative models: a more conventional model where tubulin dimers are added directly into a microtubule lattice, and one that considers an additional type of tubulin lateral interaction proposed to exist in intermediate sheet structures during the microtubule assembly process. The first model involves a single type of lateral interactions between tubulin subunits, whereas the latter considers a second type that can convert to the canonical lateral contact during microtubule closure into a cylinder. Our analysis shows that only the second model can reproduce the AFM results over a broad parameter range. We propose additional studies using different sizes of AFM tips that would allow to unambiguously distinguish the relative validity of the two models.
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