Single-molecule analysis of cadherin-mediated cell-cell adhesion.
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.
Panorchan
Porntula
P
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Thompson
Melissa S
MS
Davis
Kelly J
KJ
Tseng
Yiider
Y
Konstantopoulos
Konstantinos
K
Wirtz
Denis
D
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D006224:Cricetinae; D018625:Microscopy, Atomic Force / Q000295:instrumentation / Q000379:methods*
D015820:Cadherins; D002118:Calcium