Talk abstracts
Talk on Thursday 11:45-12:00pm submitted by Collin Nisler
Desmosomal cadherins beating under tension
Collin Nisler (Biophysics), Brandon Neel (Chemistry and Biochemistry)
Abstract:
Cadherins are ubiquitous cell-cell adhesion proteins that form a large superfamily, of which more than 126 members are present in vertebrates. The biological roles of cadherins are as diverse as the proteins themselves, which have been implicated in neuronal wiring, signaling, mechanotransduction, and adhesion in several tissue types. One class of cadherin proteins, the classical desmosomal cadherins desmoglein (DSG) and desmocollin (DSC), are found in cell-cell junctions known as the desmosome and are responsible for maintaining cardiac and epithelial tissue integrity in the presence of constant physical stresses. Here we present results from all atom molecular dynamics simulations used to investigate the dynamics and physical properties of DSG and DSC dimers. Additionally, we show results from simulations of a 1-million-atom lattice system built from individual proteins representing a potential model of the desmosome as it could exist in tissues. Using equilibrium simulations and applied force with steered molecular dynamics simulations, DSC and DSG proteins were found to exhibit soft unbending before unbinding both in their dimeric and lattice forms. Additionally, several lateral cis contacts were identified in the lattice system that affected the mechanical properties during unbinding, indicating potential important interactions that could be targeted in experiments. Overall, the simulations suggest a two-stage mechanism of unbinding and a model for how the desmosome could respond to force in vivo.
Keywords: desmosome, cadherins, molecular dynamics