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Trictide, a tricellulin‐derived peptide to overcome cellular barriers
Author(s) -
Cording Jimmi,
Arslan Basak,
Staat Christian,
Dithmer Sophie,
Krug Susanne M.,
Krüger Anneliese,
Berndt Philipp,
Günther Ramona,
Winkler Lars,
Blasig Ingolf E.,
Haseloff Reiner F.
Publication year - 2017
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13392
Subject(s) - occludin , tight junction , paracellular transport , chemistry , microbiology and biotechnology , claudin , extracellular , biophysics , biochemistry , biology , membrane , permeability (electromagnetism)
The majority of tight junction (TJ) proteins restrict the paracellular permeation of solutes via their extracellular loops (ECLs). Tricellulin tightens tricellular TJs (tTJs) and regulates bicellular TJ (bTJ) proteins. We demonstrate that the addition of recombinantly produced extracellular loop 2 (ECL2) of tricellulin opens cellular barriers. The peptidomimetic trictide, a synthetic peptide derived from tricellulin ECL2, increases the passage of ions, as well as of small and larger molecules up to 10 kDa, between 16 and 30 h after application to human epithelial colorectal adenocarcinoma cell line 2. Tricellulin and lipolysis‐stimulated lipoprotein receptor relocate from tTJs toward bTJs, while the TJ proteins claudin‐1 and occludin redistribute from bTJs to the cytosol. Analyzing the opening of the tricellular sealing tube by the peptidomimetic using super‐resolution stimulated‐emission depletion microscopy revealed a tricellulin‐free area at the tricellular region. Cis ‐interactions (as measured by fluorescence resonance energy transfer) of tricellulin–tricellulin (tTJs), tricellulin–claudin‐1, tricellulin–marvelD3, and occludin–occludin (bTJs) were strongly affected by trictide treatment. Circular dichroism spectroscopy and molecular modeling suggest that trictide adopts a β‐sheet structure, resulting in a peculiar interaction surface for its binding to tricellulin. In conclusion, trictide is a novel and promising tool for overcoming cellular barriers at bTJs and tTJs with the potential to transiently improve drug delivery.