Dynamics of the axon plasma membrane skeleton
Dynamics of the axon plasma membrane skeleton
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DOI：
10.1039/d2sm01602h
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发表时间：
2023-03-13
期刊：
影响因子：
3.4
通讯作者：
Lykotrafitis, George
中科院分区：
文献类型：
--
作者：
Chai, Zhaojie;Gu, Shiju;Lykotrafitis, George
最近通过超分辨显微镜实验发现，轴突质膜骨架(APMS)由一系列周期性排列的方位肌动蛋白环组成，这些环通过纵向光谱蛋白细丝连接起来，形成一个正交异性网络。通常的看法是APMS增强了轴突的结构稳定性，但其对轴突变形的影响尚不清楚。为了研究APMS对延伸的响应，我们引入了一个粗粒分子动力学模型，该模型由形成环的肌动蛋白颗粒和代表具有重复序列的幽灵蛋白四聚体的粒子链组成。我们观察到，力-伸长曲线的形状最初是线性的，力的大小取决于伸长率。即使在最初的变形阶段，也会出现血影蛋白重复序列的展开，但在整个APMS的情况下，在一个血影蛋白四聚体的情况下观察到的相应的力-伸展曲线的锯齿形状并不出现。其原因是，在伸展过程中，幽灵蛋白的展开在细丝之间不同步。如果肌动蛋白-血影蛋白结合保持不变，由于血影蛋白展开频率的增加，力伸展反应达到理想的可塑性区域。然而，当肌动蛋白-血影蛋白连接解离时，APMS会软化，阻力随着轴突的延长而线性下降，直到APMS完全被切断。此外，当环到环的距离在拉伸下保持固定时，由于遵循齐纳模型的Kelvin-Voigt表示的光谱蛋白四聚体的额外展开，阻力作为时间的函数而指数松弛。
It was recently revealed via super-resolution microscopy experiments that the axon plasma membrane skeleton (APMS) comprises a series of periodically arranged azimuthal actin rings connected via longitudinal spectrin filaments forming an orthotropic network. The common perception is that APMS enhances structural stability of the axon but its impact on axon deformation is unknown. To investigate the response of the APMS to extension, we introduce a coarse-grain molecular dynamics model consisting of actin particles forming rings and chains of particles representing spectrin tetramers with repeats than can unfold. We observe that the shape of force-extension curve is initially linear and the force level depends on the extension rate. Even during the initial deformation stage, unfolding of spectrin repeats occurs, but the saw-tooth shape of the corresponding force-extension curve observed in the case of one spectrin tetramer does not appear in the case of the entire APMS. The reason is that spectrin unfolding is not synchronized across filaments during extension. If actin-spectrin associations remain intact, the force-extension response reaches a perfectly plastic region because of increased spectrin unfolding frequency. However, when actin-spectrin links dissociate, which can happen at moderate and high extension rates, APMS softens and the resistance force decreases linearly as the axon elongates until it reaches a point where the APMS is completely severed. Furthermore, when the ring-to-ring distance is maintained fixed under stretch, the resistance force relaxes exponentially as a function of time due to additional unfolding of spectrin tetramers following the Kelvin-Voigt representation of the Zener model.