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.
Highlights
Cadherins are expressed in virtually all solid tissues and play a key role in a wide range of physiological and pathological processes
N-cadherin–N-cadherin and E-cadherin–E-cadherin bonds display pronounced differences in adhesion force and reactive compliance, but not in bond lifetime. Together these results suggest that classical type I N- and E-cadherins form bonds that exhibit significantly different kinetic and micromechanical properties
Analysis of cadherin-cadherin interactions in live cells at the single-molecule level Pair-wise cadherin-cadherin binding interactions on apposing cells are characterized at the single-molecule level using a molecular force probe (MFP) (Fig. 1A) (Hanley et al, 2003)
Summary
Cadherins are expressed in virtually all solid tissues and play a key role in a wide range of physiological and pathological processes. These calcium-dependent cell-surface molecules cluster at sites of cell-cell contact where they mediate cell adhesion and signaling, and subsequently influence other cell processes such as motility, differentiation and carcinogenesis (Adams and Nelson, 1998). Differential binding capacity and adhesion specificity of cadherins are thought to be responsible for the formation of tissue boundaries and cell sorting in developing tissues (Duguay et al, 2003; Gumbiner, 1996). The fundamental question of whether individual cadherin molecules display differential binding and adhesion specificity at the single-molecule level rather than the cell level, remains unanswered
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
