Dresden 2017 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 10: Posters - Single Molecule Biophysics

BP 10.7: Poster

Montag, 20. März 2017, 17:30–19:30, P3

Investigation of cardiomyopathy-related desmoglein-2 variants — •Mareike Dieding¹, Raimund Kerkhoff¹, Jana Debus², Anna Gärtner-Rommel², Volker Walhorn¹, Hendrik Milting², and Dario Anselmetti¹ — ¹Experimental Biophysics & Applied Nanoscience, Bielefeld University, Germany — ²Erich und Hanna Klessmann-Institut, Herz- und Diabeteszentrum Bad Oeynhausen, Germany

Desmoglein-2 (DSG2) is a desmosomal transmembrane glycoprotein in heart muscle cells. The homophilic interaction of its extracellular domains provide the intracellular mechanical contract between the desmosomes of adjacent cells. Variants of DSG2 are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) a rare but severe heart muscle disease. DSG2 wildtype (WT) and several variants were investigated on the cellular and the single molecule level, respectively. The adhesion of single DSG2 homo-complexes was analyzed by means of atomic force microscopy based single-molecule force spectroscopy (AFM-SMFS). Moreover, using Jarzynski's equation we estimated the difference of free energy in order to fully characterize the kinetics and thermodynamics of the homophilic DSG2 binding. Furthermore, cell-cell adhesion was analyzed using confluent monolayers of stable transfected full-length-DSG2 WT and DSG2 variant HT1080 cultures that were subjected to mechanical stress.

The results of the dissociation assay and AFM experiments consistently revealed that DSG2 variants tend to an increased cell-cell adhesion and a prolonged DSG2 bond life-time, respectively.