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Functional modeling of tight junctions in intestinal cell monolayers using polyethylene glycol oligomers

Watson, CJ, Rowland, M and Warhurst, G 2001, 'Functional modeling of tight junctions in intestinal cell monolayers using polyethylene glycol oligomers' , American Journal of Physiology - Cell Physiology, 281 (2) , C388-C397.

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Abstract

Despite significant advances in the characterization of tight junction (TJ) proteins, little is known about how molecular changes relate to function due primarily to the limitations of conventional paracellular probes. To address this, the paracellular pathway in Caco-2 and T84 cell lines was profiled by measuring the permeabilities of 24 polyethylene glycols (PEG) of increasing molecular radius (3.5-7.4 Å) analyzed by mass spectrometry. When combined with a paracellular sieving model, these data provided quantitative descriptors of the pathway under control conditions and after exposure to TJ modulators. PEG profiles in both cell lines conformed to a biphasic process involving a restrictive pore (radius 4.3-4.5 Å) and a nonrestrictive component responsible for permeability of larger molecules. PEG profiling revealed significant differences between the effects of EGTA and sodium caprate (C10). The restrictive component of EGTA-treated cells lost all size discrimination due to an increase in pore radius. Sodium caprate had no effect on pore radius but increased permeability via a different mechanism possibly involving increased numbers of functional pores. PEG profiling provides a useful tool for probing the functional regulation of the paracellular route.

Item Type: Article
Themes: Subjects / Themes > R Medicine > R Medicine (General)
Health and Wellbeing
Schools: Colleges and Schools > College of Science & Technology
Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences
Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences > Ecosystems and Environment Research Centre
Journal or Publication Title: American Journal of Physiology - Cell Physiology
Publisher: American Physiological Society
Refereed: Yes
ISSN: 0363-6143
Depositing User: H Kenna
Date Deposited: 20 Aug 2007 14:39
Last Modified: 20 Aug 2013 16:46
URI: http://usir.salford.ac.uk/id/eprint/253

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