Structural dynamics of tight junctions modulate the properties of the epithelial barrier

• DOI: 10.1371/journal.pone.0214876
• Publication Date: 2019-04-09T17:49:44Z
• Authors: Aapo Tervonen; Teemu O. Ihalainen; Soile Nymark; Jari Hyttinen
• Keywords: 570; Science; 217; Epithelium; Permeability; Cell Line; Madin Darby Canine Kidney Cells; Tight Junctions; 03 medical and health sciences; Dogs; Lääketieteen bioteknologia - Medical biotechnology; Cell Line, Tumor; Animals; Humans; Tight junctions; 0303 health sciences; Q; Resistors; R; Membrane Proteins; Epithelial Cells; 217 Medical engineering; Simulation and modeling; Oligomers; Electrical resistance; Medicine; Caco-2 Cells; Molecular structure; Research Article

Tight junctions are dynamic structures that are crucial in establishing the diffusion and electrical barrier of epithelial monolayers. Dysfunctions in the tight junctions can impede this barrier function and lead to many pathological conditions. Unfortunately, detailed understanding of the non-specific permeation pathway through the tight junctions, the so-called leak pathway, is lacking. We created computational models of the leak pathway to describe the two main barrier measures, molecular permeability and transepithelial electric resistance while using common structural dynamics. Our results showed that the proposed alternatives for the leak pathway, the bicellular strand opening dynamics and the tricellular pores, contribute together with distinct degrees, depending on the epithelium. The models can also capture changes in the tight junction barrier caused by changes in tight junction protein composition. In addition, we observed that the molecular permeability was markedly more sensitive to changes in the tight junction structure and strand dynamics compared with transepithelial electric resistance. The results highlight that our model creates a good methodological framework to integrate knowledge on the tight junction structure as well as to provide insights and tools to advance tight junction research.