Mechanical Heterogeneity Favors Fragmentation of Strained Actin Filaments
Mechanical Heterogeneity Favors Fragmentation of Strained Actin Filaments
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DOI：
10.1016/j.bpj.2015.03.058
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发表时间：
2015-05-05
影响因子：
3.4
通讯作者：
Blanchoin, Laurent
中科院分区：
文献类型：
--
作者：
De la Cruz, Enrique M.;Martiel, Jean-Louis;Blanchoin, Laurent
我们提出了一个一般模型的肌动蛋白丝变形和破碎的压力。弹性自由能密度沿着长丝是由它们的形状和机械性能，这是在弯曲，扭转，扭转弯曲耦合弹性建模。存储在细丝变形中的弹性能量（即，应变）使碎裂-退火反应自由能分布倾斜以有利于碎裂。能量梯度引入局部剪切力，加速丝亚基间键断裂。切割蛋白质，cofilin，使长丝在弯曲和扭曲时更柔顺。结果，部分用cofilin修饰的长丝是机械异质的（即，不均匀）并显示出不同于机械均匀的非对称形状变形和能量分布（即，均匀的）、裸露的肌动蛋白或饱和的cofilactin丝。局部屈曲应变取决于柔性段的相对尺寸以及侧翼区域的弯曲和扭转刚度。具有单个裸露/cofilin装饰的边界的细丝在顺应性cofilactin段内将能量和力定位在边界附近。预测具有小的cofilin簇的丝在顺应性cofilactin内而不是在边界处片段化。忽略扭曲-弯曲耦合弹性的贡献会低估能量密度和沿着细丝的梯度，从而低估细丝应变对碎裂的净效应。空间限制导致顺应性共丝肌动蛋白片段和细丝采用更高的变形模式并储存更多的弹性能量，从而促进碎片化。本文提出的理论和模拟建立了肌动蛋白丝断裂热力学和弹性之间的定量关系，并揭示了调控蛋白引入的丝机械性质的局部不连续性如何调节切割效率和沿沿着丝的位置。机械异质细丝的涌现行为，特别是在限制下，强调了细胞中的切断可能受到多种物理和化学因素的影响。
We present a general model of actin filament deformation and fragmentation in response to compressive forces. The elastic free energy density along filaments is determined by their shape and mechanical properties, which were modeled in terms of bending, twisting, and twist-bend coupling elasticities. The elastic energy stored in filament deformation (i.e., strain) tilts the fragmentation-annealing reaction free-energy profile to favor fragmentation. The energy gradient introduces a local shear force that accelerates filament intersubunit bond rupture. The severing protein, cofilin, renders filaments more compliant in bending and twisting. As a result, filaments that are partially decorated with cofilin are mechanically heterogeneous (i.e., nonuniform) and display asymmetric shape deformations and energy profiles distinct from mechanically homogenous (i.e., uniform), bare actin, or saturated cofilactin filaments. The local buckling strain depends on the relative size of the compliant segment as well as the bending and twisting rigidities of flanking regions. Filaments with a single bare/cofilin-decorated boundary localize energy and force adjacent to the boundary, within the compliant cofilactin segment. Filaments with small cofilin clusters were predicted to fragment within the compliant cofilactin rather than at boundaries. Neglecting contributions from twist-bend coupling elasticity underestimates the energy density and gradients along filaments, and thus the net effects of filament strain to fragmentation. Spatial confinement causes compliant cofilactin segments and filaments to adopt higher deformation modes and store more elastic energy, thereby promoting fragmentation. The theory and simulations presented here establish a quantitative relationship between actin filament fragmentation thermodynamics and elasticity, and reveal how local discontinuities in filament mechanical properties introduced by regulatory proteins can modulate both the severing efficiency and location along filaments. The emergent behavior of mechanically heterogeneous filaments, particularly under confinement, emphasizes that severing in cells is likely to be influenced by multiple physical and chemical factors.