The organization of actin filaments (F-actin) into crosslinked networks determines the transmission of mechanical stresses within the cytoskeleton and subsequent changes in cell and tissue shape. Principally mediated by proteins such as α-actinin, F-actin crosslinking increases both network connectivity and rigidity, thereby facilitating stress transmission at low crosslinking yet attenuating transmission at high crosslinker concentration. Here, we engineer a two-dimensional model of the actomyosin cytoskeleton, in which myosin-induced mechanical stresses are controlled by light. We alter the extent of F-actin crosslinking by the introduction of oligomerized cofilin. At pH 6.5, F-actin severing by cofilin is weak, but cofilin bundles and crosslinks filaments. Given its effect of lowering the F-actin bending stiffness, cofilin- crosslinked networks are significantly more flexible and softer in bending than networks crosslinked by α-actinin. Thus, upon local activation of myosin-induced contractile stress, the network bends out-of-plane in contrast to the in-plane compression as observed with networks crosslinked by α-actinin. Here, we demonstrate that local effects on filament mechanics by cofilin introduces novel large-scale network material properties that enable the sculpting of complex shapes in the cell cytoskeleton.

中文翻译：

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Cofilin介导的肌动蛋白丝网络灵活性促进2D至3D肌动球蛋白形状变化

肌动蛋白丝（F-肌动蛋白）组织成交联网络决定了细胞骨架内机械应力的传递以及随后细胞和组织形状的变化。 F-肌动蛋白交联主要由 α-肌动蛋白等蛋白质介导，可增加网络连接性和刚性，从而促进低交联下的应力传递，同时减弱高交联剂浓度下的传递。在这里，我们设计了肌动球蛋白细胞骨架的二维模型，其中肌球蛋白诱导的机械应力由光控制。我们通过引入寡聚肌动蛋白丝切蛋白来改变 F-肌动蛋白交联的程度。在 pH 6.5 时，肌动蛋白丝切蛋白对 F-肌动蛋白的切断作用较弱，但丝切蛋白会成束并交联丝。鉴于其降低 F-肌动蛋白弯曲刚度的作用，肌动蛋白丝切蛋白交联网络比 α-肌动蛋白交联网络在弯曲方面显着更灵活且更柔软。因此，在肌球蛋白诱导的收缩应力局部激活时，网络在平面外弯曲，这与通过 α-辅肌动蛋白交联的网络观察到的平面内压缩相反。在这里，我们证明了丝切蛋白对丝力学的局部影响引入了新颖的大规模网络材料特性，使得能够在细胞骨架中雕刻复杂的形状。