Direct molecular force measurements of multiple adhesive interactions between cadherin ectodomains

Direct-force measurements of the interactions between recombinant C-cadheri n from Xenopus demonstrated that the ectodomain of cadherin exhibits multip le adhesive contacts that involve successive domains along the extracellula r region of the protein. Contacts between the fully interdigitated antipara llel proteins form the strongest adhesive interaction. A second weaker mini mum was measured when the interdigitated proteins were separated by a dista nce equal to the length of one domain of the extracellular (EC) fragment an d corresponding to the antiparallel alignment of domains one through four ( EC1 through EC4). The successive rupture of these interactions generates an unbinding force profile that may be optimized to impede the abrupt failure of cadherin-mediated junctions under force.