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Nanotopographic cues increase epithelial paracellular permeability through cytoskeletal reorganization (780.6)
Author(s) -
Hutto Tarianna,
Ollerenshaw Jeremy,
Swarnakar Snehasikta,
Bock Suzanne,
Ross Russell,
Lillard James,
Koval Michael
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.780.6
Subject(s) - paracellular transport , microbiology and biotechnology , tight junction , chemistry , mmp9 , actin cytoskeleton , mmp2 , permeability (electromagnetism) , cytoskeleton , transcellular , actin , biophysics , cell , biology , membrane , biochemistry , downregulation and upregulation , gene
Paracellular permeability between epithelial cells is regulated by tight junctions (TJs) which act as a barrier to drug delivery across the epithelium. Previous studies (Kam et al., Nano Lett. (2013)) have found that nanostructured films (NSFs) imprinted on polypropylene (PP) with pitch spacing of 300 nm, average height of 300 nm and average diameter of 200 nm (P(1.5);DN2) increase paracellular permeability of CaCo2 colonic epithelial cells to macromolecule sized agents, independently from changes to transepithelial resistance. To define a mechanism for the effects of NSFs on CaCo2 cells, we examined changes to F‐actin by immunofluorescence (IF). Contact of CaCo2 cells with DN2 NSFs disrupted cortical actin at the plasma membrane, in contrast to non‐imprinted PP which had little effect. To determine whether matrix metalloproteases (MMPs) may be involved in this response, we examined the effect of DN2 films on expression and function of MMP2 and MMP9. By IF and in‐gel zymography, DN2 induced changes in MMP9 expression relative to MMP2. MMP9 inhibitors are being assessed to determine whether they inhibit changes to paracellular flux and actin organization induced by DN2 as a strategy to modulate NSF‐facilitated drug delivery.