Molecular Investigation of the Intestinal Barrier in Health and Disease

The intestinal epithelial barrier contributes to the absorption of nutrients and in maintaining homeostasis. Several intestinal disorders such as Crohn’s disease and Ulcerative Colitis show common pathological features corresponding to a decreased intestinal epithelial barrier function, which makes it imperative to investigate the functional units of the intestinal barriers formed by complex protein interfaces called the tight junctions. Among the diverse set of transmembrane proteins involved in the formation of tight junctions, the mal-distribution of claudin family of proteins show direct correlation to compromised barrier functioning. Interestingly, claudin-3 expression reduces drastically in compromised barriers, while an increased expression of claudin-23 is suggested to improve the barrier functions. Experimental study of membrane proteins can be time consuming and tedious. In this work, we used a computational modeling approach to investigate the nature of interfaces formed by the combination of claudin-3 and 23 to achieve a fundamental understanding of the role of claudin interfaces in intestinal barrier functions