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Ann N Y Acad Sci. 2017 Jun;1397(1):209-218. doi: 10.1111/nyas.13374. Epub 2017 Jun 12.

Dynamic modeling of the tight junction pore pathway.

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Department of Pathology, The University of Chicago, Chicago, Illinois.
Departments of Pathology and Medicine (GI), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.


Claudins define paracellular permeability to small molecules by forming ion-selective pores within the tight junction. We recently demonstrated that claudin-2 channels are gated and open and close on a submillisecond timescale. To determine if and how the ensemble behavior of this unique class of entirely extracellular gated ion channels could define global epithelial barrier function, we have developed an in silico model of local claudin-2 behavior. This model considers the complex anastomosing ultrastructure of tight junction strands and can be scaled to show that local behavior defines global epithelial barrier function of epithelial monolayers expressing different levels of claudin-2. This is the first mathematical model to describe global epithelial barrier function in terms of the dynamic behavior of single tight junction channels and establishes a framework to consider gating kinetics as a means to regulate barrier function.


claudin-2; claudins; ion channels; permeability; tight junction proteins; tight junctions

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