The Structure and Function of VE‐cadherin in Endothelial Cells

Abstract

Endothelial cells, cells that line the blood vessels, are responsible for transporting the flow of blood to tissues for the purpose of oxygenating and supplying nutrients. These cells are connected, side‐to‐side, by adherens junctions (AJs). The proteins responsible for keeping AJs together are the adhesion molecules called VE‐cadherins. The York Community High School MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine structure‐function relationships of these proteins. Each VE‐cadherin is composed of five extracellular domains, a transmembrane domain, and a cytoplasmic domain. Each domain is made up of a seven stranded beta barrel fold. One such strand is called the A strand, and this strand, in the EC1 domain, allows for two VE‐cadherins from two adjacent endothelial cells to connect together. This formation of cell‐cell adhesion between the two VE‐cadherins is due to heterophilic interaction. Disruption of VE‐cadherin‐mediated cell‐cell adhesion results in increased permeability of the endothelial cells which can cause edema and hemorrhages. There are several factors that can disrupt this VE‐cadherin‐VE‐cadherin cell adhesion event, such as bacterial infection‐induced sepsis. In the presence of an optimal concentration of calcium and magnesium, however, VE‐cadherin molecules are able to promote a type of paracellular pathway that mediates the passage of hormones, oxygen, and nutrients. VE‐cadherin is an integral protein that functions as an adhesion zipper for endothelial cells; therefore, without these adhesion molecules, the endothelium will not be able to work as a selective barrier.Support or Funding InformationCenter for BioMolecular Modeling, Milwaukee School of Engineering