Cell-substrate mechanics guide collective cell migration through intercellular adhesion: a dynamic finite element cellular model.

Abstract

During the process of tissue formation and regeneration, cells migrate collectively while remaining connected through intercellular adhesions. However, the roles of cell-substrate and cell-cell mechanical interactions in regulating collective cell migration are still unclear. In this study, we employ a newly developed finite element cellular model to study collective cell migration by exploring the effects of mechanical feedback between cell and substrate and mechanical signal transmission between adjacent cells. Our viscoelastic model of cells consists many triangular elements and is of high resolution. Cadherin adhesion between cells is modeled explicitly as linear springs at subcellular level. In addition, we incorporate a mechano-chemical feedback loop between cell-substrate mechanics and Rac-mediated cell protrusion. Our model can reproduce a number of experimentally observed patterns of collective cell migration during wound healing, including cell migration persistence, separation distance between cell pairs and migration direction. Moreover, we demonstrate that cell protrusion determined by the cell-substrate mechanics plays an important role in guiding persistent and oriented collective cell migration. Furthermore, this guidance cue can be maintained and transmitted to submarginal cells of long distance through intercellular adhesions. Our study illustrates that our finite element cellular model can be employed to study broad problems of complex tissue in dynamic changes at subcellular level.