The influence of cholesterol on self-assembly of tight junction proteins

Tight junctions exist between epithelial cells in our bodies. They are important to seal the paracellular space and act as biological barriers and allow the transport of both water and ions. Tight junctions are complex barriers that consist of many different components where claudin proteins are one of the most important for function. There are many variants of claudins and 23 have been found in humans. Dysregulation of claudin expression may lead to diseases such as Crohns and IBS. Two proteins, claudin-2 and claudin-15 are present in high amounts in the gut. They are of interest in pharmaceutical development as many drugs are absorbed in the gut. Cholesterol is present in varied amounts in our cell membranes and modifies their properties depending on the amount. The aim for this thesis is to analyze the impact cholesterol has on the self-assembly of tight junction formation in lipid bilayers (DOPC). This is done with coarse grained molecular dynamics with the Martini force field and gromacs software suite. Membranes were built with Charmm-GUI. Claudin-15 showed visible interaction between proteins in the lipid bilayerswhereas claudin-2 did not. Further analysis showed that cholesterol had impacted formation oftight junction by hindering the movement of the proteins in the membranes. To make the resultsmore impactful and reliable, more simulations need to be done.