LAUSR

Significance E-cadherin is a major cell–cell adhesion molecule that connects opposing cells via extracellular domains (ectodomains) and regulates tissue morphology and dynamics. Mutual binding of the ectodomains has been considered to be formed by a strand-swap (SS-) dimer via an X-dimer; however, the dimerization processes have not been directly visualized, and other potential dynamic interactions have been proposed. In this study, high-speed atomic force microscopy (HS-AFM), mutational analyses, and structural modeling revealed the dimeric structures that are mainly classified into SS- (W-shaped), X-like (cross-shaped), and S-shaped (or reverse S-shaped) dimers. The structural transition from the S-shaped and X-like dimers to the SS-dimer formation, visualized by HS-AFM, suggests the contribution of dynamic interactions to the SS-dimer formation of E-cadherin in solution.