# Molecular Mechanisms Underlying E-cadherin Mechanotransduction

> **NIH NIH R35** · UNIVERSITY OF IOWA · 2021 · $378,121

## Abstract

PROJECT SUMMARY
All cells and organisms are subjected to mechanical forces. These forces are sensed by cell surface receptors,
such as the epithelial (E)-cadherin, which links cells to their neighbors. E-cadherin responds to force by
activating signaling pathways inside the cell. These pathways trigger the formation of new cell-cell adhesions
and stimulate the rearrangement and reinforcement of the actin cytoskeleton. These actin cytoskeletal
rearrangements are energetically costly. We recently discovered that the energy required to fuel the
cytoskeletal rearrangements is provided by AMP-activated protein kinase (AMPK). AMPK is a master regulator
of metabolism. It is activated when force is applied to E-cadherin and signals for ATP. The ATP produced fuels
the cytoskeletal changes necessary for cells to resist external forces. Thus, AMPK is mechanosensitive and
links E-cadherin mechanotransduction to energy homeostasis. Using biochemical, biophysical, and cell
biological approaches, in this proposal we will develop a paradigm for how mechanotransduction and
metabolism are coordinated. We will identify how: (1) glucose is taken up into the cell in response to force, (2)
metabolism and reinforcement of the actin cytoskeletal are spatially coordinated, (3) different magnitudes of
force impact cell mechanics, and (4) forces relayed from E-cadherin adjust global cellular metabolism. Through
this work, we intend to provide a fundamentally new picture of the interconnected pathways that govern
mechanotransduction. This new paradigm can be applied to better understand other mechanosensitive
systems. Additionally, it will inform the nature of disease defects and define strategies to prevent metabolic
disturbances.

## Key facts

- **NIH application ID:** 10151668
- **Project number:** 5R35GM136291-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Kris A DeMali
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,121
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151668

## Citation

> US National Institutes of Health, RePORTER application 10151668, Molecular Mechanisms Underlying E-cadherin Mechanotransduction (5R35GM136291-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10151668. Licensed CC0.

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