Soheilypour Mohammad, Peyro Mohaddeseh, Peter Stephen J, Mofrad Mohammad R K
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, Berkeley, California.
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, Berkeley, California.
Biophys J. 2015 Apr 7;108(7):1718-1726. doi: 10.1016/j.bpj.2015.01.030.
As the major structural constituent of the cytoskeleton, microtubules (MTs) serve a variety of biological functions that range from facilitating organelle transport to maintaining the mechanical integrity of the cell. Neuronal MTs exhibit a distinct configuration, hexagonally packed bundles of MT filaments, interconnected by MT-associated protein (MAP) tau. Building on our previous work on mechanical response of axonal MT bundles under uniaxial tension, this study is focused on exploring the compression scenarios. Intracellular MTs carry a large fraction of the compressive loads sensed by the cell and therefore, like any other column-like structure, are prone to substantial bending and buckling. Various biological activities, e.g., actomyosin contractility and many pathological conditions are driven or followed by bending, looping, and buckling of MT filaments. The coarse-grained model previously developed in our lab has been used to study the mechanical behavior of individual and bundled in vivo MT filaments under uniaxial compression. Both configurations show tip-localized, decaying, and short-wavelength buckling. This behavior highlights the role of the surrounding cytoplasm and MAP tau on MT buckling behavior, which allows MT filaments to bear much larger compressive forces. It is observed that MAP tau interconnections improve this effect by a factor of two. The enhanced ability of MT bundles to damp buckling waves relative to individual MT filaments, may be interpreted as a self-defense mechanism because it helps axonal MTs to endure harsher environments while maintaining their function. The results indicate that MT filaments in a bundle do not buckle simultaneously implying that the applied stress is not equally shared among the MT filaments, that is a consequence of the nonuniform distribution of MAP tau proteins along the bundle length. Furthermore, from a pathological perspective, it is observed that axonal MT bundles are more vulnerable to failure in compression than tension.
作为细胞骨架的主要结构成分，微管（MTs）具有多种生物学功能，从促进细胞器运输到维持细胞的机械完整性。神经元微管呈现出独特的结构，即由微管相关蛋白（MAP）tau相互连接的六边形排列的微管丝束。基于我们之前关于轴突微管束在单轴拉伸下的力学响应的研究，本研究聚焦于探索压缩情况。细胞内的微管承担了细胞所感知到的大部分压缩负荷，因此，像任何其他柱状结构一样，容易发生显著的弯曲和屈曲。各种生物活动，例如肌动球蛋白收缩性以及许多病理状况，都是由微管丝的弯曲、成环和屈曲所驱动或随之发生的。我们实验室之前开发的粗粒度模型已被用于研究体内单个和束状微管丝在单轴压缩下的力学行为。两种结构均显示出尖端局部化、衰减且波长较短的屈曲。这种行为突出了周围细胞质和MAP tau对微管屈曲行为的作用，这使得微管丝能够承受更大的压缩力。据观察，MAP tau的连接使这种效果提高了两倍。相对于单个微管丝，微管束抑制屈曲波的能力增强，这可以被解释为一种自我防御机制，因为它有助于轴突微管在维持其功能的同时承受更恶劣的环境。结果表明，束状微管丝不会同时发生屈曲，这意味着施加的应力在微管丝之间并非均匀分担，这是由于MAP tau蛋白沿束长度的分布不均匀所致。此外，从病理学角度来看，观察到轴突微管束在压缩时比在拉伸时更容易失效。
