Molecular Control of Cellular Adhesion Using Catch Bonds

The goal of this study was to investigate the possibility of catch bond formation between nectin and actin during cellular adhesion by modeling the actin-filament binding protein, afadin, out of equilibrium. This was done through the in silico methodology of Molecular Dynamics (MD); more specifically using Steered Molecular Dynamics (SMD) and Replica Exchange Molecular Dynamics (REMD). The methodology of this experiment centered around generating physiologically probable structures through REMD, then using MD and SMD methods to generate structures in the absence and presence of force respectively. These structures were then analyzed through Solvent Accessible Surface Area (SASA) measurements to assess the overall compactness of the structure, which led to implicit observations on the overall resistance of force that this structure has. Overall, it was found that the structure displayed more compact conformations in the presence of force as the SASA values of the binding pocket and individual residues involved in the system tend to decrease as force was applied. This is indicative of more stable conformations and a force resistant quality that is indicative of catch bonding, thus leading to the natural conclusion that this structure displays catch bond character.