Figure 1.

(A) Crystal structure of Dsg2 homodimer shown in ribbon representation [¹², pdbID: 5ERD]. Coordinated Ca²⁺ are shown as blue spheres. (B) Schematic of cantilever tip and sample substrate functionalized with Dsg2 for AFM single molecule force spectroscopy. Both, cantilever and substrate are modified with covalently immobilized Dsg2 fragments. (C) SMFS working principle and typical force-distance cycle exposing a specific dissociation event. The striated area under the curve represents the dissipated work to break a Dsg2 homodimer. (D) Principle of dispase assay for measuring cell-cell adhesion. Cells grown to confluency (a) are lifted up by dispase treatment and exposed to mechanical stress by shaking of cell cultures. Resulting islets of the monolayer are counted and recombinant cell cultures of mutant and wildtype are compared (b).