Poster abstracts

Poster number 50 submitted by Collin Nisler

Exploring the mechanics of desmosomal cadherins using all atom and coarse grained molecular dynamics simulations

Collin Nisler (Biophysics)

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 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 tissue integrity in the presence of constant physical stresses. All atom and coarse grained molecular dynamics simulations have been used to investigate the dynamics and physical properties of DSG and DSC. The simulations consist of combinations of DSC and DSG dimers, as well as a lattice built from individual proteins comprising more than 3 million atoms that represents a potential structure of the desmosome as it could exist in tissues. Using equilibrium and steered molecular dynamics simulations, DSC and DSG were found to exhibit unbending before unbinding both in their dimeric and lattice form, resulting in a two-stage mechanism of unbinding. Additionally, the ability of the lattice to return to its initial conformation after being pulled was explored using a coarse grained model of the desmosomal lattice.

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Keywords: Molecular Dynamics, Cadherins, Desmosome