# Mechanoregulation of E-cadherin Adhesion

> **NIH NIH R15** · OLD DOMINION UNIVERSITY · 2020 · $449,783

## Abstract

Project Summary
E-cadherin is the primary mediator of strong cell-cell adhesion between epithelial cells and plays an
essential role in the morphogenesis and maintenance of epithelial tissues. E-cadherin adhesion is
modulated by multiple biochemical and biophysical cues. The long term goal of the project is to understand
how the mechanical regulation of E-cadherin adhesion leads to a cohesive yet dynamic multi-cellular
architecture in epithelial tissues. The goal of the proposed project is to uncover how the epithelial cell-
specific viscoelastic microenvironment of E-cadherin modulates its adhesion and how E-cadherin-
dependent Rho GTPase activity and tension in turn modulate this viscoelasticity. Firstly, E-cadherin is
known to be a mechanosensor and resides in a microenvironment formed by the adjoining epithelial cells.
However, how epithelial cell-like viscoelastic properties modulate E-cadherin adhesion is not known.
Secondly, it is not clear how E-cadherin dependent biochemical signals in turn modulate its
microenvironmental viscoelasticity. In particular, the effect of Rho and Rac, known modulators of the actin
cytoskeleton, on E-cadherin microenvironment viscoelastic properties is unclear. This effect is essential to
understand in order to delineate the role of these Rho GTPases in mediating cell-cell contact formation.
Thirdly, E-cadherin adhesions transmit cell-generated as well as external forces imposed on epithelial
tissues. How the level of this tension transmitted across cells determines the viscoelastic properties close to
cell-cell junctions is unknown. Knowledge of cell viscoelastic properties near cell-cell junctions is important
not only to understand E-cadherin mechanobiology, but more generally to also understand cell deformation
in response to forces transmitted at cell-cell adhesions. We will use an array of tools including E-cadherin
biomimetic substrates with tunable viscoelastic properties similar to epithelial cells, flow assays with such E-
cadherin soft substrates, magnetic pulling cytometry and high resolution traction force microscopy in the
presence and absence of external stretch, to answer these questions at the sub-cellular, cellular and supra-
cellular levels. Results of the proposed project will be crucial in understanding the context-dependent
biophysical control of E-cadherin adhesion. Knowledge gained from the project will be essential to better
understand the functional basis of the role of E-cadherin in mediating epithelial tissue integrity, mechanical
coherence and its dysregulation in disease states like cancer.

## Key facts

- **NIH application ID:** 10113715
- **Project number:** 2R15GM116082-02
- **Recipient organization:** OLD DOMINION UNIVERSITY
- **Principal Investigator:** Venkat Maruthamuthu
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,783
- **Award type:** 2
- **Project period:** 2015-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113715

## Citation

> US National Institutes of Health, RePORTER application 10113715, Mechanoregulation of E-cadherin Adhesion (2R15GM116082-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10113715. Licensed CC0.

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