Institute for Biophysical Dynamics, James Franck Institute, University of Chicago, Chicago, IL 60637, USA.
Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):20820-5. doi: 10.1073/pnas.1214753109. Epub 2012 Dec 3.
Here we develop a minimal model of the cell actomyosin cortex by forming a quasi-2D cross-linked filamentous actin (F-actin) network adhered to a model cell membrane and contracted by myosin thick filaments. Myosin motors generate both compressive and tensile stresses on F-actin and consequently induce large bending fluctuations, which reduces their effective persistence length to <1 μm. Over a large range of conditions, we show the extent of network contraction corresponds exactly to the extent of individual F-actin shortening via buckling. This demonstrates an essential role of buckling in breaking the symmetry between tensile and compressive stresses to facilitate mesoscale network contraction of up to 80% strain. Portions of buckled F-actin with a radius of curvature ~300 nm are prone to severing and thus compressive stresses mechanically coordinate contractility with F-actin severing, the initial step of F-actin turnover. Finally, the F-actin curvature acquired by myosin-induced stresses can be further constrained by adhesion of the network to a membrane, accelerating filament severing but inhibiting the long-range transmission of the stresses necessary for network contractility. Thus, the extent of membrane adhesion can regulate the coupling between network contraction and F-actin severing. These data demonstrate the essential role of the nonlinear response of F-actin to compressive stresses in potentiating both myosin-mediated contractility and filament severing. This may serve as a general mechanism to mechanically coordinate contractility and cortical dynamics across diverse actomyosin assemblies in smooth muscle and nonmuscle cells.
在这里，我们通过形成一个准二维交联丝状肌动蛋白（F-actin）网络来构建一个细胞肌动球蛋白皮质的最小模型，该网络附着在模型细胞膜上，并由肌球蛋白粗丝收缩。肌球蛋白马达在 F-actin 上产生压缩和拉伸应力，从而导致大的弯曲波动，从而将其有效持久长度降低到<1μm。在很大的条件范围内，我们表明网络收缩的程度与通过屈曲的单个 F-actin 缩短的程度完全对应。这证明了屈曲在打破拉伸和压缩应力之间的对称性以促进高达 80%应变的介观网络收缩方面的重要作用。曲率半径约为 300nm 的弯曲 F-actin 部分容易被切断，因此压缩应力通过 F-actin 切断来机械协调收缩性，这是 F-actin 周转的初始步骤。最后，由肌球蛋白诱导的应力获得的 F-actin 曲率可以通过网络与膜的粘附进一步限制，加速细丝切断，但抑制网络收缩所需的应力的长程传递。因此，膜粘附的程度可以调节网络收缩和 F-actin 切断之间的耦合。这些数据表明 F-actin 对压缩应力的非线性响应在增强肌球蛋白介导的收缩性和细丝切断方面起着重要作用。这可能是一种通用机制，可以在平滑肌和非肌肉细胞中各种肌动球蛋白组件中机械协调收缩性和皮质动力学。
