Structural dynamics of tight junctions modulate the properties of the epithelial barrier
| Autor: | Aapo, Tervonen, Teemu O, Ihalainen, Soile, Nymark, Jari, Hyttinen |
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| Přispěvatelé: | Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, Tampere University, BioMediTech, Research group: Computational Biophysics and Imaging Group, Doctoral Programme in Biomedical Sciences and Engineering, Research group: Biophysics of the eye |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Science
Resistors Membrane Proteins Epithelial Cells 217 Medical engineering Permeability Epithelium Simulation and modeling Cell Line Madin Darby Canine Kidney Cells Tight Junctions Dogs Cell Line Tumor Oligomers Lääketieteen bioteknologia - Medical biotechnology Electrical resistance Animals Humans Medicine Caco-2 Cells Tight junctions Molecular structure |
| Zdroj: | PLoS ONE, Vol 14, Iss 4, p e0214876 (2019) |
| Popis: | 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. publishedVersion |
| Databáze: | OpenAIRE |
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