Poster abstracts

Poster number 39 submitted by Brandon Neel

Towards probing the release of signal factors from the adherens junction by molecular dynamics simulations

Brandon L. Neel (OSBP), Marcos Sotomayor (Department of Chemistry & Biochemistry)

Abstract:
The adherens junction in animal epithelia is a ubiquitous cell-cell contact formed by classical members of the cadherin superfamily. Tension modulates the formation and maintenance of adherens junctions, which dynamically respond to changes in force originating both extra- and intra-cellularly. These junctions provide a strong adhesion between cells with the cytoplasmic portion of epithelial cadherin (Ecad), the main cadherin of the junction, binding to and sequestering multiple cell-proliferation signaling molecules. Here we present a model of the complete adherens junction based on available experimental and crystallographic data. The model includes Ecad with proper cis- and trans-bonds with other Ecad molecules; a phosphatidylcholine cell membrane; phosphorylation modifications of the cytoplasmic Ecad domain; as well as p120-catenin, β-catenin, α-catenin, vinculin, and f-actin. All the connections between protein pairs were modeled after available structures. The complete model of the adherens junction, in excess of 4 million atoms, is now ready for large-scale molecular dynamics simulations, both with and without tension. We expect that forces applied to the junction will alter the orientation of associated cytoplasmic proteins and that our simulations will provide insight into the initial steps of signal release.

Keywords: Cell Adhesion, Structure, Computational