Theoretical and computational modelling of cell-cell adhesion

Cell-cell adhesion and decohesion are important in biology, to keep cellular tissues together and, in addition, to allow the disengagement of cells during remodeling. Due to the fluid nature of the surface of animal cells, the molecular bonds that keep cells together are laterally mobile. These molecular bonds form clusters, attach to the cytoskeleton through mechanosensitive adapter protein molecules, and undergo turnover by endocytosis. Cells can tune various properties of these molecular bonds including diffusivity, stiffness, and force sensitivity. We lack a fundamental understanding of how mechanics, chemistry, and biological regulation integrate to support the adaptable function of cell-cell adhesion, and how effective mechanical properties of adhesions such as strength and toughness depend on the molecular properties of bonds. The main objective is to develop a mathematical and computational model for cell-cell adhesion in full 3D generality coupling the active gel model of the actomyosin cortex to the adhesion dynamics of cell adhesion molecules of the Cadherins family. It allows us to understand how the actin cortex and the adhesion complexes work together to give rise to adaptable junctions and how the self-organization of the adhesion complexes takes place. We show how the interplay of mechanics and chemistry at adhesion patches leads to a wide range of behaviors that cells can use to stabilize cell-cell junctions during physiological stretch or to selectively detach during morphogenesis.