Biomechanics of actin filaments: A computational multi-level study
Biomechanics of actin filaments: A computational multi-level study
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DOI：
10.1016/j.jbiomech.2010.11.014
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发表时间：
2011-02-24
影响因子：
2.4
通讯作者：
Morbiducci, Umberto
中科院分区：
文献类型：
--
作者：
Deriu, Marco A.;Bidone, Tamara C.;Morbiducci, Umberto
肌动蛋白微丝(F-肌动蛋白)是细胞骨架的结构和功能成分。尽管F-肌动蛋白在细胞力学中起着主要作用，但它的力学行为仍未完全被研究。在本研究中，F-肌动蛋白的力学性质与其构筑单体(G-肌动蛋白)的分子拓扑结构有关。利用平衡分子动力学(MD)模拟和简正波分析(NMA)相结合的方法，对长度可达500 nm的F-肌动蛋白进行了建模和表征。对生理条件下G-肌动蛋白的分子重排进行了分子动力学模拟：用NMA方法从F-肌动蛋白的振动模式计算其宏观性质，结果表明弯曲刚度、弯曲弹性系数和持续长度与F-肌动蛋白的长度无关。相反，选定的G-肌动蛋白残基的取向和运动在决定细丝柔韧性方面起着主要作用。总之，本研究(I)证明了MD和NMA的联合计算方法允许在考虑细丝的分子拓扑(即G-肌动蛋白的分子构象)的情况下研究F-肌动蛋白的生物力学，以及(Ii)这可以仅使用结晶学G-肌动蛋白来完成，不需要引入实验参数也不需要减少残基的数量。(C)2010爱思唯尔有限公司。保留所有权利。
The actin microfilament (F-actin) is a structural and functional component of the cell cytoskeleton. Notwithstanding the primary role it plays for the mechanics of the cell, the mechanical behaviour of F-actin is still not totally explored. In particular, the relationship between the mechanics of F-actin and its molecular architecture is not completely understood.In this study, the mechanical properties of F-actin were related to the molecular topology of its building monomers (G-actin) by employing a computational multi-level approach. F-actins with lengths up to 500 nm were modelled and characterized, using a combination of equilibrium molecular dynamics (MD) simulations and normal mode analysis (NMA). MD simulations were performed to analyze the molecular rearrangements of G-actin in physiological conditions: NMA was applied to compute the macroscopic properties of F-actin from its vibrational modes of motion.Results from this multi-level approach showed that bending stiffness, bending modulus and persistence length are independent from the length of F-actin. On the contrary, the orientations and motions of selected groups of residues of G-actin play a primary role in determining the filament flexibility.In conclusion, this study (i) demonstrated that a combined computational approach of MD and NMA allows to investigate the biomechanics of F-actin taking into account the molecular topology of the filament (i.e., the molecular conformations of G-actin) and (ii) that this can be done using only crystallographic G-actin, without the need of introducing experimental parameters nor of reducing the number of residues. (C) 2010 Elsevier Ltd. All rights reserved.