Novak Igor L, Slepchenko Boris M, Mogilner Alex
Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Biophys J. 2008 Aug;95(4):1627-38. doi: 10.1529/biophysj.108.130096. Epub 2008 May 23.
Cell migration is based on an actin treadmill, which in turn depends on recycling of G-actin across the cell, from the rear where F-actin disassembles, to the front, where F-actin polymerizes. To analyze the rates of the actin transport, we used the Virtual Cell software to solve the diffusion-drift-reaction equations for the G-actin concentration in a realistic three-dimensional geometry of the motile cell. Numerical solutions demonstrate that F-actin disassembly at the cell rear and assembly at the front, along with diffusion, establish a G-actin gradient that transports G-actin forward "globally" across the lamellipod. Alternatively, if the F-actin assembly and disassembly are distributed throughout the lamellipod, F-/G-actin turnover is local, and diffusion plays little role. Chemical reactions and/or convective flow of cytoplasm of plausible magnitude affect the transport very little. Spatial distribution of G-actin is smooth and not sensitive to F-actin density fluctuations. Finally, we conclude that the cell body volume slows characteristic diffusion-related relaxation time in motile cell from approximately 10 to approximately 100 s. We discuss biological implications of the local and global regimes of the G-actin transport.
细胞迁移基于肌动蛋白踏车模型，而这又依赖于球形肌动蛋白（G-肌动蛋白）在细胞内的循环利用，即从丝状肌动蛋白（F-肌动蛋白）解聚的细胞后部，转运至F-肌动蛋白聚合的细胞前部。为了分析肌动蛋白的运输速率，我们使用虚拟细胞软件，在运动细胞的真实三维几何结构中求解G-肌动蛋白浓度的扩散-漂移-反应方程。数值解表明，细胞后部的F-肌动蛋白解聚和前部的组装，以及扩散作用，共同建立了一个G-肌动蛋白梯度，该梯度将G-肌动蛋白“整体地”向前运输穿过片状伪足。另外，如果F-肌动蛋白的组装和解聚分布在整个片状伪足中，F-/G-肌动蛋白的周转是局部性的，扩散作用则很小。合理量级的化学反应和/或细胞质对流对运输的影响非常小。G-肌动蛋白的空间分布是平滑的，且对F-肌动蛋白密度波动不敏感。最后，我们得出结论，细胞体体积使运动细胞中与扩散相关的特征弛豫时间从大约10秒减缓至大约100秒。我们讨论了G-肌动蛋白运输的局部和整体机制的生物学意义。
