Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA.
Wiley Interdiscip Rev Syst Biol Med. 2011 Mar-Apr;3(2):231-40. doi: 10.1002/wsbm.110.
Dissecting the intracellular signaling mechanisms that govern the movement of eukaryotic cells presents a major challenge, not only because of the large number of molecular players involved, but even more so because of the dynamic nature of their regulation by both biochemical and mechanical interactions. Computational modeling and analysis have emerged as useful tools for understanding how the physical properties of cells and their microenvironment are coupled with certain biochemical pathways to actuate and control cell motility. In this focused review, we highlight some of the more recent applications of quantitative modeling and analysis in the field of cell migration. Both in modeling and experiment, it has been prudent to follow a reductionist approach in order to characterize what are arguably the principal modules: spatial polarization of signaling pathways, regulation of the actin cytoskeleton, and dynamics of focal adhesions. While it is important that we 'cut our teeth' on these subsystems, focusing on the details of certain aspects while ignoring or coarse-graining others, it is clear that the challenge ahead will be to characterize the couplings between them in an integrated framework.
解析真核细胞运动的细胞内信号机制是一项重大挑战，不仅因为涉及到大量的分子成分，更因为它们的调控受到生化和力学相互作用的动态影响。计算建模和分析已经成为理解细胞及其微环境的物理特性如何与某些生化途径偶联以启动和控制细胞运动的有用工具。在这篇重点综述中，我们强调了定量建模和分析在细胞迁移领域的一些最新应用。无论是在建模还是实验中，采用还原论方法来表征可以说是主要模块都是明智的：信号通路的空间极化、肌动蛋白细胞骨架的调节和黏着斑的动力学。虽然我们在这些子系统上“磨练”很重要，专注于某些方面的细节，而忽略或粗化其他方面，但很明显，未来的挑战将是在一个集成框架中描述它们之间的耦合。
