Single-molecule analysis of cadherin-mediated cell-cell adhesion

Abstract

Cadherins are ubiquitous cell surface molecules that are expressed in virtually all solid tissues and localize at sites of cell-cell contact. Cadherins form a large and diverse family of adhesion molecules, which play a crucial role in a multitude of cellular processes, including cell-cell adhesion, motility, and cell sorting in maturing organs and tissues, presumably because of their different binding capacity and specificity. Here, we develop a method that probes the biochemical and biophysical properties of the binding interactions between cadherins expressed on the surface of living cells, at the single-molecule level. Single-molecule force spectroscopy reveals that classical cadherins, N-cadherin and E-cadherin, form bonds that display adhesion specificity, and a pronounced difference in adhesion force and reactive compliance, but not in bond lifetime. Moreover, their potentials of interaction, derived from force-spectroscopy measurements, are qualitatively different when comparing the single-barrier energy potential for the dissociation of an N-cadherin-N-cadherin bond with the double-barrier energy potential for an E-cadherin-E-cadherin bond. Together these results suggest that N-cadherin and E-cadherin molecules form homophilic bonds between juxtaposed cells that have significantly different kinetic and micromechanical properties.