Physics

Kinetics

Cell

Cadherin

Heart failure

Biology

Gene

Cardiology

Psychology

Affect (linguistics)

Chemistry

Cardiomyopathy

Mutation

Quantum mechanics

Communication

Genetics

Medicine

Journal of Cardiology and Cardiovascular Sciences

Cadherins are calcium dependent adhesion proteins that bridge the intercellular gap and establish a tight connection to adjacent cells.Desmoglein-2 (DSG2) is a specific cadherin of the cell-cell contact in cardiac desmosomes.Mutations in the DSG2 gene are associated with rare but severe heart muscle diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC).However, the molecular pathomechanism of many DSG2 mutations is unknown.In our recently published research, we report on the homophilic binding properties of wildtype DSG2 and two mutations thereof.We found that wildtype DSG2 binding kinetics differs significantly from the two analyzed mutations whereas thermodynamic properties such as the difference in Gibbs free energy are virtually unaffected.Here, we comment on (bio-) physical concepts how non-covalent bonds are characterized and we highlight the limitations of these concepts.Furthermore, we consistently link molecular binding properties of DSG2 with the macroscopic stability of cellular networks overexpressing a distinct DSG2 species.Finally, on the basis of DSG2 binding kinetics, we draft a biophysically inspired hypothesis of a molecular pathomechanism leading to ARVC.

Commentary: Arrhythmogenic Cardiomyopathy Related DSG2 Mutations Affect Cadherin Binding Kinetics