# Investigating E-cadherin Mechanotransduction

> **NIH NIH F31** · UNIVERSITY OF IOWA · 2021 · $19,058

## Abstract

Project Summary/Abstract
 All cells experience force. These forces are sensed by cell surface adhesion receptors and trigger robust
actin cytoskeletal rearrangements and growth of the associated adhesion complex to counter the applied forces.
This process is known as cell stiffening or reinforcement. The actin re-arrangements necessary for stiffening are
energetically costly suggesting that mechanisms coupling force transduction and energy production exist.
Previously our laboratory identified a mechanism for coupling force transmission and energy utilization. We
demonstrated that, in response to force, AMPK is recruited and activated at the E-cadherin adhesion complexes,
thereby stimulating actomyosin contractility, glucose uptake, and ATP production. This increase in glucose
uptake and ATP provides the energy necessary to grow the adhesion complexes and reinforce the actin
cytoskeleton. Despite this advancement, how mechanical force modulates glucose uptake and glucose
metabolism is not fully understood. This study aims to determine how glucose transporter-1 (GLUT1) affects
force-induced metabolic changes and cell stiffening. Here we suggest that GLUT1 is the force-sensitive glucose
transporter responsible for the glucose uptake necessary for the growth of adhesion complexes and
reinforcement of the actin cytoskeleton. In further support of this notion, we show that GLUT1 is recruited to the
cell-cell junctions and forms a complex with E-cadherin in response to force. Furthermore, we present evidence
that inhibition of GLUT1 blocks force-induced cell stiffening. A second goal of the proposed work in this study is
to assess how glucose metabolism is coupled to E-cadherin mediated cytoskeleton rearrangements. Multiple
glycolytic enzymes are bound to filamentous actin (F-actin), such as aldolase and phosphofructokinase-1.
Previous studies have demonstrated that F-actin bound aldolase is released upon insulin stimulated actin
remodeling. We propose that the application of force to E-cadherin causes the release of F-actin-bound glycolytic
enzymes, such as aldolase and PFK. Additionally, we suspect that cytosolic release of these enzymes mediates
the increase and localization of glycolysis, necessary for force-induced energy production. This study proposes
a novel connection between glucose metabolism and the energy-intensive process of force-induced cell
stiffening.

## Key facts

- **NIH application ID:** 10201518
- **Project number:** 5F31GM135962-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Alicia Salvi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $19,058
- **Award type:** 5
- **Project period:** 2020-01-21 → 2021-07-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201518

## Citation

> US National Institutes of Health, RePORTER application 10201518, Investigating E-cadherin Mechanotransduction (5F31GM135962-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201518. Licensed CC0.

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