Role of Multiple Bonds Between the Single Cell Adhesion Molecules, Nectin and Cadherin, Revealed by High Sensitive Force Measurements

Nectins and cadherins, members of cell adhesion molecules (CAMs), are the primary mediators for various types of cell–cell junctions. Here, intermolecular force microscopy (IFM) with force sensitivity at sub-picoNewtons is used to characterize the extracellular trans-interactions between paired nectins and paired cadherins at the single molecule level. Three and four different bound states between paired nectins and paired cadherins are, respectively, identified and characterized based on bond strength distributions where each bound state has a unique lifetime and bond length. The results indicate that multiple domains of nectins act uncooperatively, as a zipper-like multiply bonded system whereas those of cadherins act cooperatively, as a parallel-like multiply bonded system, consistent with a “fork initiation and zipper” hypothesis for the formation of cell–cell adhesion. The observed dynamic properties among multiple bonds are expected to be advantageous such that nectins search adaptively in the cell–cell exploratory recognition process while cadherins slowly stabilize in the cell–cell zippering process.