Chai Zhaojie, Gu Shiju, Lykotrafitis George
Department of Mechanical Engineering, University of Connecticut, Storrs, CT 06269, USA.
Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, USA.
Soft Matter. 2023 Apr 5;19(14):2514-2528. doi: 10.1039/d2sm01602h.
It was recently revealed super-resolution microscopy experiments that the axon plasma membrane skeleton (APMS) comprises a series of periodically arranged azimuthal actin rings connected 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.
最近通过超分辨率显微镜实验发现，轴突质膜骨架（APMS）由一系列周期性排列的方位角肌动蛋白环组成，这些环与纵向血影蛋白丝相连，形成一个正交各向异性网络。普遍的看法是，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对伸展的响应，我们引入了一个粗粒度分子动力学模型，该模型由形成环的肌动蛋白颗粒和代表血影蛋白四聚体的颗粒链组成，血影蛋白四聚体具有可展开的重复序列。我们观察到，力-伸展曲线的形状最初是线性的，力的大小取决于伸展速率。即使在初始变形阶段，血影蛋白重复序列也会发生展开，但在单个血影蛋白四聚体的情况下观察到的相应力-伸展曲线的锯齿形状在整个APMS的情况下并未出现。原因是在伸展过程中，血影蛋白的展开在各丝之间并不同步。如果肌动蛋白-血影蛋白结合保持完整，由于血影蛋白展开频率增加，力-伸展响应会达到一个完全塑性区域。然而，当肌动蛋白-血影蛋白连接解离时（这可能在中等和高伸展速率下发生），APMS会变软，并且随着轴突伸长，阻力会线性下降，直到达到APMS完全断裂的点。此外，当在拉伸下环与环之间的距离保持固定时，由于遵循齐纳模型的开尔文-沃伊特表示的血影蛋白四聚体的额外展开，阻力会随时间呈指数松弛。
