Single Molecule AFM Force Spectroscopy - PHYSICS OF MOLECULAR RECOGNITION

Contact: Dr. Volker Walhorn

    Research Topic: The physical mechanisms of specific, non-covalent intermolecular binding is quantitatively investigated by single-molecule (dynamic) force spectroscopy with atomic force microscopy (AFM), optical tweezers (OT) and magnetic tweezers (MT). Here, specific molecular forces, elasticities, kinetic reaction rate constants (lifetimes) and the energy landscape of the molecular binding potential is measured by AFM at the single-molecule level in vitro on isolated but functional complexes. Nowadays, these specific interactions can be scrutinized in a quantitative manner at the sensitivity level on single-point mutations (nucleic acids, amino acids) allowing single-molecule affinity ranking in a broad affinity range of 0,1 mM-1 fM revealing distinct differences in the binding properties and mechanisms. Over the last years, special emphasis has been put on so-called molecular catch-bond systems that were observed when investigating the interplay of human sulfatates (Sulf1, Sulf2) with glycosaminoglycans (heparan sulfate, heparin, dermatan sulfate, ...) in cell signaling cascades. In addition, we recently explored the homophilic interaction mechanisms between desmosomal desmoglein-2 (DSG2) and mutations thereof that play an important role for the integrity of mechanically active cells like cardiomyocytes.
    Images: Single molecule force spectroscopy methodology (left), dynamic AFM force-spectroscopy-plots (middle left), atomistic model for peptide-DNA interaction (middle right), and the result of a quantum chemistry calculation for a supramolecular host-guest-complex (right).
    References: ... see section Publications

Last updated: 06.03.2017