Center for Theoretical Biological Physics and Department of Physics, University of California, San Diego, La Jolla, CA 92093-0374, USA.
Proc Natl Acad Sci U S A. 2012 May 1;109(18):6851-6. doi: 10.1073/pnas.1203252109. Epub 2012 Apr 9.
Cell migration is a pervasive process in many biology systems and involves protrusive forces generated by actin polymerization, myosin dependent contractile forces, and force transmission between the cell and the substrate through adhesion sites. Here we develop a computational model for cell motion that uses the phase-field method to solve for the moving boundary with physical membrane properties. It includes a reaction-diffusion model for the actin-myosin machinery and discrete adhesion sites which can be in a "gripping" or "slipping" mode and integrates the adhesion dynamics with the dynamics of the actin filaments, modeled as a viscous network. To test this model, we apply it to fish keratocytes, fast moving cells that maintain their morphology, and show that we are able to reproduce recent experimental results on actin flow and stress patterns. Furthermore, we explore the phase diagram of cell motility by varying myosin II activity and adhesion strength. Our model suggests that the pattern of the actin flow inside the cell, the cell velocity, and the cell morphology are determined by the integration of actin polymerization, myosin contraction, adhesion forces, and membrane forces.
细胞迁移是许多生物学系统中普遍存在的过程,涉及到由肌动蛋白聚合产生的突起力、肌球蛋白依赖性收缩力以及通过黏附位点在细胞和基质之间传递的力。在这里,我们开发了一种用于细胞运动的计算模型,该模型使用相场方法来求解具有物理膜性质的运动边界。它包括一个用于肌动球蛋白机械的反应扩散模型和离散的黏附位点,这些黏附位点可以处于“夹持”或“滑动”模式,并将黏附动力学与肌动蛋白丝的动力学结合起来,将肌动蛋白丝建模为粘性网络。为了测试这个模型,我们将其应用于快速移动的鱼角膜细胞,这些细胞能够保持其形态,并展示了我们能够重现最近关于肌动蛋白流和应力模式的实验结果。此外,我们通过改变肌球蛋白 II 的活性和黏附强度来探索细胞迁移的相图。我们的模型表明,细胞内肌动蛋白流的模式、细胞速度和细胞形态是由肌动蛋白聚合、肌球蛋白收缩、黏附力和膜力的整合决定的。