Stability of Cell-Cell Junctions: Balancing Cortical Tension and Cadherin Aggregation at cell interface during cell-cell separation.

The mechanobiology of cell-cell adhesion is important in determining the rheology and dynamics of tissues. Two quantities, adhesion energy—arising from cadherin binding between cells, and cortical tension—arising from the actomyosin cortex, play a major role in self-organization of cells and the mechanical integrity of tissues. Using Dual Pipette Aspiration, the separation force of cell doublets was observed to be more dependent on cortical tension at the cell-cell interface than adhesion energy. To understand this phenomenon, we examine a minimal "two-body problem" of cells theoretically. We show how such tension reduction can lead to a robust cell junction. As cadherin is tethered to the cortex, the decrease in contact radius during the pull-off process leads to localization of cadherin. Which leads to an adaptive strengthening of the junction under external force and hence a larger separation force. Furthermore, we determine the junction rupture kinetics using the bond lifetimes of cadherin-cadherin bonds quantified in various AFM studies. Even with such a simple model, our results can aid in more accurate physical modeling of tissues used to study problems ranging from embryonic development to pathological conditions, including how tissues resist tearing and fracture.