Wang Xinxin, Carlsson Anders E
Department of Bioinformatics, UT Southwestern Medical Center, Dallas, Texas, United States of America.
Department of Physics and NSF Center for Engineering MechanoBiology, Washington University, St. Louis, Missouri, United States of America.
PLoS Comput Biol. 2017 Dec 14;13(12):e1005901. doi: 10.1371/journal.pcbi.1005901. eCollection 2017 Dec.
We present a Master Equation approach to calculating polymerization dynamics and force generation by branched actin networks at membranes. The method treats the time evolution of the F-actin distribution in three dimensions, with branching included as a directional spreading term. It is validated by comparison with stochastic simulations of force generation by actin polymerization at obstacles coated with actin "nucleation promoting factors" (NPFs). The method is then used to treat the dynamics of actin polymerization and force generation during endocytosis in yeast, using a model in which NPFs form a ring around the endocytic site, centered by a spot of molecules attaching the actin network strongly to the membrane. We find that a spontaneous actin filament nucleation mechanism is required for adequate forces to drive the process, that partial inhibition of branching and polymerization lead to different characteristic responses, and that a limited range of polymerization-rate values provide effective invagination and obtain correct predictions for the effects of mutations in the active regions of the NPFs.
我们提出了一种主方程方法,用于计算膜上分支肌动蛋白网络的聚合动力学和力的产生。该方法处理三维空间中F-肌动蛋白分布的时间演化,将分支作为一个定向扩散项包含在内。通过与在涂有肌动蛋白“成核促进因子”(NPFs)的障碍物上肌动蛋白聚合产生力的随机模拟进行比较,验证了该方法。然后,使用一个模型,其中NPFs在内吞位点周围形成一个环,以将肌动蛋白网络强烈附着在膜上的分子点为中心,该方法用于处理酵母内吞过程中肌动蛋白聚合和力产生的动力学。我们发现,需要一种自发的肌动蛋白丝成核机制来提供足够的力来驱动该过程,分支和聚合的部分抑制会导致不同的特征响应,并且有限范围的聚合速率值可提供有效的内陷,并对NPFs活性区域突变的影响获得正确的预测。