MODELING CELL-CELL ADHESION WITH A CADHERIN BASED MODEL

Cell-cell adhesion is critical in morphogenesis, tissue formation, cancer, and wound healing. A better understanding of cell-cell adhesion mediated by cadherins will allow all these processes to be mimicked and manipulated to achieve desired objectives. This paper investigates the role of the actin structure associated with cadherin adhesion sites. It is clear that the actin cytoskeleton is dynamic and undergoes many changes as cells adhere to one another. The purpose of the changes is unclear. It has been thought that the actin structure anchor the cadherin complexes in the membrane limiting their diffusion and providing structural reinforcement for the complexes. It is also possible that the actin filaments move the cadherin complexes to desired locations and or help force the cell membrane out to allow more cell-cell contacts. A mathematical model was developed to investigate these questions [1]. Using the immersed boundary method and modeling the forces and motion of the cadherin complexes in the membrane, insight into the purpose of the actin cytoskeleton restructuring was gained. A mathematical model was used to examine the basic biophysical parameters that must exist for cells to initiate and expand their cell-cell junctions. The immersed boundary (IB) method was used to model individual cells that display an elastic, deformable cortex. Cells coated with cadherins adhered to one another and expanded their junctions to a maximum area. Using this method, we independently tested the roles of actin in cadherin anchoring or membrane protrusion formation in expansion of cell-cell contacts to a maximum cell-cell junction area. The immersed boundary represented the cell membrane and the associated cortical shell. The cadherins are modeled as discrete sites which may or may not move freely in the membrane or along the boundary points of the immersed boundary. The immerse boundary method solves the Navier-Stokes equations to determine the motion of the membrane and the membrane exert forces on the surrounding fluid [2]. The model predicts that the cadherin anchoring is not necessary to form or stabilize cell-cell contacts for cells in suspension. In fact, allowing the cadherin complexes to free diffuse in the membrane or fixing them in the membrane does not affect the overall outcome of the cell-cell adhesion for suspended cells. REFERENCE