RT Journal Article
SR Electronic
T1 Nanotopography enhances dynamic remodeling of tight junction proteins through cytosolic complexes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 858118
DO 10.1101/858118
A1 Huang, Xiao
A1 Shi, Xiaoyu
A1 Hansen, Mollie Eva
A1 Nemeth, Cameron L.
A1 Ceili, Anna
A1 Huang, Bo
A1 Mauro, Theodora
A1 Koval, Michael
A1 Desai, Tejal A.
YR 2019
UL http://biorxiv.org/content/early/2019/11/28/858118.abstract
AB The epithelial tight junction regulates barrier function and is responsive to extracellular stimuli. Here we demonstrated that contact of synthetic surfaces with defined nanotopography at the apical surface of epithelial monolayers increased paracellular permeability of macromolecules. To monitor changes in tight junction morphology in live cells, we fluorescently tagged the scaffold protein zonula occludens-1 (ZO-1) through CRISPR/Cas9-based gene editing. Contact between cells and nanostructured surfaces destabilized junction-associated ZO-1 and promoted its arrangement into highly dynamic non-junctional cytosolic complexes that averaged ∼2 μm in diameter. Junction-associated ZO-1 rapidly remodeled, and we also observed the direct transformation of cytosolic complexes into junction-like structures. Claudin-family tight junction transmembrane proteins and F-actin also were associated with these ZO-1 containing cytosolic complexes. These data suggest that the cytosolic structures are novel intermediates formed in response to nanotopographic cues that facilitate rapid tight junction remodeling in order to regulate paracellular permeability.