Geometrical nonlinear elasticity of axon under tension: A coarse-grained computational study
Geometrical nonlinear elasticity of axon under tension: A coarse-grained computational study
复制标题
张力下轴突的几何非线性弹性：粗粒度计算研究
DOI：
10.1016/j.bpj.2021.07.019
复制
发表时间：
2021
影响因子：
3.4
通讯作者：
Wang, Xianqiao
中科院分区：
文献类型：
--
作者：
Liu, Ning;Chavoshnejad, Poorya;Li, Shaoheng;Razavi, Mir Jalil;Liu, Tianming;Pidaparti, Ramana;Wang, Xianqiao
轴突束由微管相关蛋白(Microtubule，MT)相关蛋白交叉连接，并以壳骨架为边界，对神经元的正常功能至关重要。了解复杂的几何参数对其力学性能的影响有助于从生物力学的角度了解轴突的神经功能，从而了解轴突结构失效引起的脑功能障碍。在这里，通过系统地调节MT长度、轴突横截面半径和tau蛋白间距，在珠-弹簧粗粒模型中研究了由tau蛋白交联的MT束的拉伸力学性质。我们的结果表明，轴突的应力-应变曲线可以分为两个区域，一个是以刚体类MT间滑动为主的非线性弹性区域，另一个是以tau蛋白和MT的仿射变形为主的线弹性区域。从能量分析来看，首先，tau蛋白主导着轴突在拉伸状态下的力学性能。在非线性区域，tau蛋白经历的不是伸长，而是类似刚体的旋转运动；而在非线性弹性区域，tau蛋白经历了沿MT轴的柔性伸长变形。第二，当相邻tau蛋白沿MT轴向的平均间距从25 nm增加到125 nm时，轴突的杨氏模数呈线性下降，而平均间距从125 nm到175 nm变化，随后达到平台值并有稳定的波动。第三，MT束横截半径的增大导致轴突的杨氏模数减小，这可能是由于每横截面MT数目的减少所致。总体而言，我们的研究结果为理解几何参数对MT束力学的影响提供了一个新的视角，并为开发潜在的医疗应用的人工MT复合体提供了理论基础。
Axon bundles cross-linked by microtubule (MT) associate proteins and bounded by a shell skeleton are critical for normal function of neurons. Understanding effects of the complexly geometrical parameters on their mechanical properties can help gain a biomechanical perspective on the neurological functions of axons and thus brain disorders caused by the structural failure of axons. Here, the tensile mechanical properties of MT bundles cross-linked by tau proteins are investigated by systematically tuning MT length, axonal cross-section radius, and tau protein spacing in a bead-spring coarse-grained model. Our results indicate that the stress-strain curves of axons can be divided into two regimes, a nonlinear elastic regime dominated by rigid-body like inter-MT sliding, and a linear elastic regime dominated by affine deformation of both tau proteins and MTs. From the energetic analyses, first, the tau proteins dominate the mechanical performance of axons under tension. In the nonlinear regime, tau proteins undergo a rigid-body like rotating motion rather than elongating, whereas in the nonlinear elastic regime, tau proteins undergo a flexible elongating deformation along the MT axis. Second, as the average spacing between adjacent tau proteins along the MT axial direction increases from 25 to 125 nm, the Young's modulus of axon experiences a linear decrease whereas with the average space varying from 125 to 175 nm, and later reaches a plateau value with a stable fluctuation. Third, the increment of the cross-section radius of the MT bundle leads to a decrease in Young's modulus of axon, which is possibly attributed to the decrease in MT numbers per cross section. Overall, our research findings offer a new perspective into understanding the effects of geometrical parameters on the mechanics of MT bundles as well as serving as a theoretical basis for the development of artificial MT complexes potentially toward medical applications.