(772h) Physical Role of E-Cadherin Mediated Cell-Cell Adherent Junctions in Multicellular Motility

Cell migration is one of the hallmarks for the metastatic process in cancer. Single cell migration has been extensively studied and different models have been proposed to understand cell motility processes. It has been suggested that metastasis may involve collective cell migration and invasion. However, the physical mechanisms of multicellular cell migration remain to be elucidated. In this work, we adopt both experimental and computational approaches to elucidate the physical role of E-Cadherin mediated cell-cell adherent junction in multicellular migration. To study the cell migration with contacts with other cells, we maintained human breast epithelial cells, the MCF-10A, and transformed metastatic breast cancer cells, MDA-MB-231, in a semi-confluent condition and observed their motility patterns. Thousands of cell movements were tracked for each condition. Our result shows that cell velocity decreases with increase of cell-cell contacts for MCF-10A cells. The same phenomenon was not found on MDA-MB-231 cells. Further, cells present the elevated correlated velocity when they are in proximity.  Both these multicellular associated phenomena are associated with E-Cadherin mediated adherent junctions since overexpression of E-cadherin in MDA-MB-231 or knockdown of a-catenin in MCF-10A will change these profiles accordingly. Based on these observations, we developed a computational model for multicellular cell motility in which we introduces intercellular drag force and velocity association caused by neighboring cells into the persistent random walk model. We validated our model by predicting motility behavior for monolayer of MCF-10A cells. Together, we have identified the principal characteristics of multicellular motility for normal and malignant breast epithelium cells. Our results reveal fundamental physical mechanism of multicellular migration and how they arise from cell-cell interactions.