Tubulin bond energies and microtubule biomechanics determined from nanoindentation in silico.
Tubulin bond energies and microtubule biomechanics determined from nanoindentation in silico.
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DOI：
10.1021/ja506385p
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发表时间：
2014-12-10
影响因子：
15
通讯作者：
Barsegov, Valeri
中科院分区：
文献类型：
--
作者：
Kononova, Olga;Kholodov, Yaroslav;Theisen, Kelly E.;Marx, Kenneth A.;Dima, Ruxandra I.;Ataullakhanov, Fazly I.;Grishchuk, Ekaterina L.;Barsegov, Valeri
微管是染色体分离机制的主要组成部分，通过微管蛋白亚基之间的纵向和横向非共价键来稳定。然而，人们对这些键的热力学和微管的物理化学性质了解甚少。在这里，我们使用多尺度计算模型和连续微管碎片的纳米压痕在硅上探索微管聚合物的生物力学。模拟和实验力-变形光谱之间的密切匹配使我们能够将微管生物力学与纳米尺度上的动态结构转变联系起来。我们的力学测试表明，压缩后的MT表现为通过横向和纵向弹性键网络相互连接的刚性元件系统。在微管连续弹性变形的初始状态之后是过渡状态，在过渡状态下，微管晶格经历了离散的结构变化，其中首先是横向键的可逆解离，然后是纵向键的不可逆解离。我们测定了微管蛋白-微管蛋白横向键（6.9±0.4 kcal/mol）和纵向键（14.9±1.5 kcal/mol）的解离自由能。这些数值与获得的微管原丝的大弯曲刚度（18,000-26,000 pN·nm2）相结合，支持了分解微管能够在细胞分裂过程中产生巨大的机械力来移动染色体的观点。我们的计算模型提供了一个全面的定量平台，将分子微管特性与微管的生理行为联系起来。硅纳米压痕方法的发展为探索其他细胞骨架和多蛋白组件的生物力学特性提供了有力的工具。
Microtubules, the primary components of the chromosome segregation machinery, are stabilized by longitudinal and lateral noncovalent bonds between the tubulin subunits. However, the thermodynamics of these bonds and the microtubule physicochemical properties are poorly understood. Here, we explore the biomechanics of microtubule polymers using multiscale computational modeling and nanoindentations in silico of a contiguous microtubule fragment. A close match between the simulated and experimental force–deformation spectra enabled us to correlate the microtubule biomechanics with dynamic structural transitions at the nanoscale. Our mechanical testing revealed that the compressed MT behaves as a system of rigid elements interconnected through a network of lateral and longitudinal elastic bonds. The initial regime of continuous elastic deformation of the microtubule is followed by the transition regime, during which the microtubule lattice undergoes discrete structural changes, which include first the reversible dissociation of lateral bonds followed by irreversible dissociation of the longitudinal bonds. We have determined the free energies of dissociation of the lateral (6.9 ± 0.4 kcal/mol) and longitudinal (14.9 ± 1.5 kcal/mol) tubulin–tubulin bonds. These values in conjunction with the large flexural rigidity of tubulin protofilaments obtained (18,000–26,000 pN·nm2) support the idea that the disassembling microtubule is capable of generating a large mechanical force to move chromosomes during cell division. Our computational modeling offers a comprehensive quantitative platform to link molecular tubulin characteristics with the physiological behavior of microtubules. The developed in silico nanoindentation method provides a powerful tool for the exploration of biomechanical properties of other cytoskeletal and multiprotein assemblies.
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影响因子：
3.4
作者：
Kononova, Olga;Snijder, Joost;Barsegov, Valeri
通讯作者：
Barsegov, Valeri
影响因子：
7.5
作者：
Bakhoum, Samuel F.;Compton, Duane A.
通讯作者：
Compton, Duane A.
影响因子：
5.6
作者：
Grafmueller, Andrea;Noya, Eva G.;Voth, Gregory A.
通讯作者：
Voth, Gregory A.
影响因子：
4
作者：
Bowne-Anderson, Hugo;Zanic, Marija;Kauer, Monika;Howard, Jonathon
通讯作者：
Howard, Jonathon
DOI：
10.1073/pnas.0806113105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Dima, Ruxandra I.;Joshi, Harshad
通讯作者：
Joshi, Harshad