The Daily Bulletin Archive

Please join the Chemistry and Physics departments for the seminar "Targeting Claudin 1 Interactions to Alter Tight-Junction Function," presented by Elizabeth Anderson, visiting assistant professor of chemistry at Skidmore College, on Tuesday, March 14, at 12:30 p.m. in Science and Mathematics Complex 170.  All students, faculty, and staff are welcome. This seminar is partially funded by the Faculty-Student Association.

Abstract
Tight junctions (TJ) prevent the diffusion of environmental chemicals, antigens, and pathogens through the paracellular space between epithelial cells. The ability to transiently alter barrier function in the epidermis could facilitate needle-free vaccine delivery. In skin, expression of the Claudin 1 (Cldn1) protein determines the strength of the TJ barrier, and peptides that mimic Cldn1 sequences can alter epithelial barrier function. We synthesized Cldn1-mimics and their scrambled analogs and discovered that in bronchial epithelial cells (16HBE cells), they disrupt TJs in a dose-dependent manner at concentrations at least an order of magnitude lower than previous reports for similar Cldn1-based sequences. When formulated with surfactant, these mimics form self-assembled, amyloid-like cross-b structures, as seen by circular dichroism, FTIR spectroscopy, and x-ray powder diffraction. These structured mimics also cause changes in the expression patterns of Cldn1 and occludin (both transmembrane TJ components) in cell culture. Importantly, these structured Cldn1 mimics caused no apparent cytotoxicity, and barrier function recovered when the peptide was removed. Future work will identify key determinants in extracellular Cldn1 interactions to guide design of the next generation of structured mimics to target TJ barrier function.