# Anti-integrin nanowires as a platform to determine mechanisms regulating transepithelial permeability

> **NIH NIH F31** · EMORY UNIVERSITY · 2020 · $45,520

## Abstract

ABSTRACT
Epithelia form selective barriers that compartmentalize organs and protect them from external environments
which allows for specialized physiologic function. Epithelial barrier permeability has two regulated components,
the transcellular path mediated by transcytosis, and the paracellular path between cell-cell contact sites
regulated by tight junctions (TJs). We previously determined that stimulation of epithelial cells by contact between
the apical plasma membrane with nanostructured films (NSFs) increases transepithelial permeability to large
macromolecules, such as Alexa-594 labeled Fab, through both the transcellular and paracellular pathways.
Several lines of evidence identified a potential role for apically localized 1 integrin in the ability of NSFs to
increase substrate permeability. However, a drawback to using NSFs is that they act by engaging large,
heterogeneous patches of the apical plasma membrane making it difficult to precisely define molecular
mechanisms linking specific surface proteins to changes in epithelial barrier function. Thus, to specifically
investigate whether 1 integrin is directly involved in increased barrier permeability, we developed an anti-
integrin nanowire system consisting of anti-1 integrin antibodies conjugated to functionalized polycaprolactone
nanowires. These anti-integrin nanowires served as a platform to specifically cluster apically localized 1 integrin
to determine whether integrin stimulation has the capacity to regulate epithelial barrier function. Treatment of
epithelial monolayers with anti-integrin nanowires significantly decreased the transepithelial resistance of the
monolayer and increased the rate of transepithelial flux of Alexa-594 Fab across polarized monolayers. These
functional effects were associated with nanowire-induced changes in the localization of the TJ scaffolding protein
zonula occludens-1 (ZO-1) and the integrin-associated actin binding protein talin, as well as rearrangement of
the actin cytoskeleton from stress fibers into a more cortical pattern of organization. In order to define the
mechanisms of action for integrin-mediated regulation of epithelial permeability we will test the hypothesis that
integrin clustering by anti-integrin nanowires increases permeability through changes in integrin-
associated actin binding proteins leading to cytoskeletal remodeling through the following Aims. In Aim 1,
we will measure the transcellular and paracellular contributions to solute permeability following integrin
stimulation by measuring how anti-integrin nanowire treatment causes structural and functional changes in TJs
and transcellular permeability. In Aim 2, we will determine if integrin mediated changes in permeability are driven
by changes in the recruitment of integrin-associated actin binding proteins and measure their impact on actin
organization. We will also assess if changes in integrin-associated actin binding proteins and actin cytoskeleton
organization ar...

## Key facts

- **NIH application ID:** 9988219
- **Project number:** 5F31GM130112-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Raven Peterson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988219

## Citation

> US National Institutes of Health, RePORTER application 9988219, Anti-integrin nanowires as a platform to determine mechanisms regulating transepithelial permeability (5F31GM130112-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9988219. Licensed CC0.

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