MULTISCALE TWO-DIMENSIONAL MODELING OF A MOTILE SIMPLE-SHAPED CELL.

Cell crawling is an important biological phenomenon underlying coordinated cell movement in morphogenesis, cancer, and wound healing. In recent decades the process of cell crawling has been experimentally and theoretically dissected into further subprocesses: protrusion of the cell at its leading edge, retraction of the cell body, and graded adhesion. A number of one-dimensional (1-D) models explain successfully a proximal-distal organization and movement of the motile cell. However, more adequate two-dimensional (2-D) models are lacking. We propose a multiscale 2-D computational model of the lamellipodium (motile appendage) of a simply shaped, rapidly crawling fish keratocyte cell. We couple submodels of (i) protrusion and adhesion at the leading edge, (ii) the elastic 2-D lamellipodial actin network, (iii) the actin-myosin contractile bundle at the rear edge, and (iv) the convection-reaction-diffusion actin transport on the free boundary lamellipodial domain. We simulate the combined model numerically using a finite element approach. The simulations reproduce observed cell shapes, forces, and movements and explain some experimental results on perturbations of the actin machinery. This novel 2-D model of the crawling cell makes testable predictions and posits questions to be answered by future modeling.