Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States of America.
Bioengineering, Pennsylvania State University, State College, PA, United States of America.
PLoS Comput Biol. 2018 Sep 17;14(9):e1006344. doi: 10.1371/journal.pcbi.1006344. eCollection 2018 Sep.
Filamentous actin (F-actin) and non-muscle myosin II motors drive cell motility and cell shape changes that guide large scale tissue movements during embryonic morphogenesis. To gain a better understanding of the role of actomyosin in vivo, we have developed a two-dimensional (2D) computational model to study emergent phenomena of dynamic unbranched actomyosin arrays in the cell cortex. These phenomena include actomyosin punctuated contractions, or "actin asters" that form within quiescent F-actin networks. Punctuated contractions involve both formation of high intensity aster-like structures and disassembly of those same structures. Our 2D model allows us to explore the kinematics of filament polarity sorting, segregation of motors, and morphology of F-actin arrays that emerge as the model structure and biophysical properties are varied. Our model demonstrates the complex, emergent feedback between filament reorganization and motor transport that generate as well as disassemble actin asters. Since intracellular actomyosin dynamics are thought to be controlled by localization of scaffold proteins that bind F-actin or their myosin motors we also apply our 2D model to recapitulate in vitro studies that have revealed complex patterns of actomyosin that assemble from patterning filaments and motor complexes with microcontact printing. Although we use a minimal representation of filament, motor, and cross-linker biophysics, our model establishes a framework for investigating the role of other actin binding proteins, how they might alter actomyosin dynamics, and makes predictions that can be tested experimentally within live cells as well as within in vitro models.
丝状肌动蛋白（F-actin）和非肌肉肌球蛋白 II 马达驱动细胞运动和细胞形状变化，这些变化指导胚胎形态发生过程中的大规模组织运动。为了更好地理解肌动球蛋白在体内的作用，我们开发了一个二维（2D）计算模型来研究细胞皮层中动态无分支肌动球蛋白阵列的突发现象。这些现象包括肌动球蛋白的点状收缩，或在静止的 F-actin 网络中形成的“actin 星状体”。点状收缩涉及高强度星状结构的形成和相同结构的解体。我们的 2D 模型使我们能够探索细丝极性排序、马达分离以及 F-actin 阵列形态的运动学，这些都是随着模型结构和生物物理特性的变化而出现的。我们的模型展示了细丝重组和马达运输之间复杂的突发反馈，这些反馈既产生又分解 actin 星状体。由于细胞内肌动球蛋白动力学被认为是由绑定 F-actin 或其肌球蛋白马达的支架蛋白的定位控制的，因此我们还将我们的 2D 模型应用于模拟体外研究，这些研究揭示了从图案化细丝和带有微接触印刷的马达复合物组装而成的复杂肌动球蛋白模式。尽管我们使用了细丝、马达和交联剂生物物理学的最小表示形式，但我们的模型为研究其他肌动蛋白结合蛋白的作用、它们如何改变肌球蛋白动力学以及做出可以在活细胞和体外模型中进行实验测试的预测建立了一个框架。
