Modeling the mechanics of cell-cell junction formation and dynamics in vascular networks*

Abstract: The dynamics and stability of cell-cell junctions plays an important role in various physiological processes, ranging from morphogenesis to cancer. In developing vascular networks, in particular, endothelial junction formation and dynamics govern the overall structure and thereby function of the vasculature.  Therefore, it is crucial to understand how the formation and subsequent evolution of cell-cell adhesion junctions are controlled by single-cell behaviors such as cell migration, cell protrusion, polarization, and cell-cell interactions mediated by mechanics or chemical sensing . Starting with a simple case of a two-body problem of cells, we study the mechanics of junction formation and how it is controlled by protrusive activity and cell-cell interactions. We further show how the feedback between cadherin bond kinetics at the cell-cell junction and actomyosin contractile forces determine the long-term junction stability. We then generalize our model to larger numbers of cells to study network formation and remodeling. Using such mechano-chemical models, one can gain insights into how cell-cell junctions affect the mechanical integrity and network topology of tissues.