Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut.
Department of Chemistry, New York University, New York, New York.
Biophys J. 2019 Aug 6;117(3):453-463. doi: 10.1016/j.bpj.2019.06.018. Epub 2019 Jun 25.
The assembly of actin filaments and filament networks generate forces that drive cell and vesicle movement. These structures and the comprising actin filaments must be mechanically stable to sustain these forces and maintain their structural integrity. Filaments in these dynamic structures must also be disassembled to recycle and replenish the pool of actin monomers available for polymerization. Actin-severing proteins such as cofilin and contractile myosin motor proteins fragment these nominally stable structures. We developed a mesoscopic-length-scale actin filament model to investigate force-induced filament fragmentation. We show that fragmentation in our model occurs at curvatures similar to previous measurements of fragmentation within (cofil)actin and actin-cofilactin boundaries. Boundaries between bare and cofilin-decorated segments are brittle and fragment at small bending and twisting deformations. Extending filaments disperses strain uniformly over subunit interfaces, and filaments fragment with no detectable partial rupture or plastic deformation. In contrast, bending or twisting filaments imposes nonuniform interface strain and leads to partial interface rupture, accelerating filament fragmentation. As a result, the rupture force under compressive loads is an order of magnitude lower than under tensile loads. Partial interface rupture may be a primary mechanism of accelerating actin filament fragmentation by other actin-destabilizing proteins.
肌动蛋白丝和丝网络的组装产生驱动细胞和囊泡运动的力。这些结构和组成的肌动蛋白丝必须具有机械稳定性，以承受这些力并保持其结构完整性。这些动态结构中的丝还必须解聚以回收和补充可用于聚合的肌动蛋白单体池。肌动蛋白丝切割蛋白（如丝切蛋白和收缩性肌球蛋白马达蛋白）会使这些名义上稳定的结构发生片段化。我们开发了一个介观长度尺度的肌动蛋白丝模型来研究力诱导的丝片段化。我们表明，在我们的模型中，片段化发生在类似于以前在（丝切蛋白）肌动蛋白和肌动蛋白-丝切蛋白边界内的片段化测量的曲率处。裸丝和丝切蛋白修饰段之间的边界在小弯曲和扭转变形下是脆性的，会发生片段化。延伸丝将应变均匀地分布在亚基界面上，并且丝没有检测到明显的部分断裂或塑性变形而发生片段化。相比之下，弯曲或扭曲的丝会在界面上产生不均匀的应变，导致部分界面断裂，从而加速丝的片段化。因此，在压缩载荷下的断裂力比在拉伸载荷下低一个数量级。部分界面断裂可能是其他肌动蛋白不稳定蛋白加速肌动蛋白丝片段化的主要机制。
