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BP: Fachverband Biologische Physik

BP 17: Poster Session II

BP 17.62: Poster

Dienstag, 18. März 2025, 18:00–20:30, P4

Human cardiac cadherin desmocollin 2 reveals ideal-, slip- and catch bonds in vitro — •Manuel Göz¹, Greta Pohl², Sylvia Steinecker¹, Volker Walhorn¹, Hendrik Milting², and Dario Anselmetti¹ — ¹Experimental Biophysics & Applied Nanoscience, Faculty of Physics, Bielefeld University, Bielefeld, Germany — ²Heart & Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany

Desmosomal cadherins like DSC2 are known to associate in a strand-swap binding motif in which an N-terminal tryptophan residue binds into the hydrophobic binding pocket of opposing cadherins. Although this binding pattern is highly specific, it is of low affinity and exhibits decreased bond lifetimes at a single-molecule level. Using AFM-based SMFS, we show that the strand-swap dimerized DSC2 has two further binding modes, which may play a role in the integrity of the cardiac muscle. At short interaction times, the DSC2 monomers associate only short-lived and force-independent. These ideal bonds are probably a precursor state that stabilizes the formation of the strand-swap dimer. Tryptophan added to the measurement buffer acts as a competitive inhibitor, preventing the N-terminal strand exchange. Here, DSC2 dimerizes as an X-dimer and shows a triphasic slip-catch-slip type of dissociation. Within a force-activated transition (catch) regime, DSC2 dimers switch between brittle low force and strengthened high force adhesion states. So we can assume that desmosomal adhesion is mediated not only by strand-swap dimers (slip bond) but also by their precursor states (ideal bond) and force-activated X-dimers (catch bond).

Keywords: Atomic force microscopy (AFM); Single molecule force spectroscopy (SMFS); Desmocollin 2 (DSC2); Two-state-two-pathway model (TSTP model); X-dimers