Modeling the Mechanical Response of Microtubule Lattices to Pressure
Modeling the Mechanical Response of Microtubule Lattices to Pressure
复制标题
模拟微管晶格对压力的机械响应
DOI：
10.1021/acs.jpcb.1c01770
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Dima, Ruxandra I.
中科院分区：
文献类型：
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作者：
Szatkowski, Lukasz;Varikoti, Rohith Anand;Dima, Ruxandra I.
微管是细胞骨架中最大、最坚硬的细丝，它必须很好地适应细胞的高度拥挤，才能发挥它们的多种功能。此外，涉及微管的基本过程，如维持细胞形状和细胞运动，已知高度依赖于外部压力。鉴于压力对微管功能的重要性，许多研究询问了这些细胞骨架细丝对渗透压的反应，这是由渗透压引起的，如聚乙二醇/聚环氧乙烷(PEO)分子或直接施加压力。对实验的解释通常是基于这样的假设，即聚乙二醇分子与微管晶格具有不利的相互作用，并且微管在压力下的行为可以用连续模型来描述。我们直接探讨了这两个假设。首先，我们使用对接和分子动力学模拟相结合的方法表征了微管细丝中的主要界面与不同大小的聚乙二醇分子之间的相互作用。其次，我们使用考虑晶格界面断裂的粗粒模型研究了微管细丝对压缩的响应。我们的结果表明，中等长度的聚乙二醇单分子不会改变微管横向界面的能量，而是靶向并能穿透这些界面上的微管蛋白单体之间的空隙，从而导致在压力下横向界面的迅速丧失。在与高渗透压相对应的条件下压缩微管会导致实验中发现的变形相的形成。我们的模拟表明，变形的原因是横向界面的断裂，而不是从连续模型推断的灯丝的屈曲。
Microtubules, the largest and stiffest filaments of the cytoskeleton, have to be well adapted to the high levels of crowdedness in cells to perform their multitude of functions. Furthermore, fundamental processes that involve microtubules, such as the maintenance of the cellular shape and cellular motion, are known to be highly dependent on external pressure. In light of the importance of pressure for the functioning of microtubules, numerous studies interrogated the response of these cytoskeletal filaments to osmotic pressure, resulting from crowding by osmolytes, such as poly(ethylene glycol)/poly(ethylene oxide) (PEG/PEO) molecules, or to direct applied pressure. The interpretation of experiments is usually based on the assumptions that PEG molecules have unfavorable interactions with the microtubule lattices and that the behavior of microtubules under pressure can be described by using continuous models. We probed directly these two assumptions. First, we characterized the interaction between the main interfaces in a microtubule filament and PEG molecules of various sizes using a combination of docking and molecular dynamics simulations. Second, we studied the response of a microtubule filament to compression using a coarse-grained model that allows for the breaking of lattice interfaces. Our results show that medium length PEG molecules do not alter the energetics of the lateral interfaces in microtubules but rather target and can penetrate into the voids between tubulin monomers at these interfaces, which can lead to a rapid loss of lateral interfaces under pressure. Compression of a microtubule under conditions corresponding to high osmotic pressure results in the formation of the deformed phase found in experiments. Our simulations show that the breaking of lateral interfaces, rather than the buckling of the filament inferred from the continuous models, accounts for the deformation.