Homophilic interaction and deformation of E-cadherin and cadherin 7 probed by single molecule force spectroscopy

• At the molecular level, the bond between E-cad is stronger than Cad 7.
• Force-strengthening of homophilic binding of E-cad, but absent in case of Cad 7.
• Unbinding forces of cadherins overlap with unfolding forces of their EC domains.
• At a stretching force ∼5 pN, EC domains of E-cad unfold in ∼30 s.
• Forced-deformation of EC domains is expected to help the strengthening of binding.

Cadherin-mediated adhesion plays a crucial role in multicellular organisms. Dysfunction within this adhesion system has major consequences in many pathologies, including cancer invasion and metastasis. However, mechanisms controlling cadherin recognition and adhesive strengthening are only partially understood. Here, we investigated the homophilic interactions and mechanical stability of the extracellular (EC) domains of E-cadherin and cadherin 7 using atomic force microscopy and magnetic tweezers. Besides exhibiting stronger interactions, E-cadherin also showed more efficient force-induced self-strengthening of interactions than cadherin 7. In addition, the distributions of the unbinding forces for both cadherins partially overlap with those of the unfolding forces, indicating that partial unfolding/deformation of the cadherin EC domains may take place during their homophilic interactions. These conformational changes may be involved in cadherins physiology function and contribute to the significant differences in adhesive strength mediated by type I and type II cadherins.