# Mechanisms of Mechanotransduction by LIM Domain Proteins

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2023 · $393,174

## Abstract

Project Summary
Mechanisms of Mechanotransduction by LIM Domain Proteins
Mechanical forces are essential to controlling the shape, movement and even many
aspects of cell physiology. Changes in the environment mechanics or defects in cellular
mechanoresponse are implicated in a plethora of diseases including atherosclerosis,
heart failure and cancer. A major challenge is to understand mechanotransduction - the
mechanisms by which mechanical information is detected and communicated to
pathways that control cell behavior. The LIM super family of proteins, which contain one
or more LIM domains, represents a large number of putative mechanosensitive cellular
proteins that are involved in physiological mechanotransduction pathways.
Understanding how the LIM domains function to detect and transmit information about
mechanical stress will result in a deeper understanding of mechanotransduction-based
signaling, which is important for developing strategies of disease treatment and organ
regeneration.
This proposal leverages an innovative combination of cell biophysics, biochemistry
molecular cell biology, live cell imaging and mathematical modeling to investigate the
mechanism by which LIM domains sense mechanical stimuli in the actin cytoskeleton
and, in turn, initiate YAP/TAZ mechanotransduction signaling. We recently discovered
that a large number of LIM domains exhibit force-sensitive binding to actin filaments. Here
we propose to: (1) identify the mechanism by which LIM proteins are recruited to
mechanically stressed actin filaments, (2) determine how the LIM sequence enables
specificity in force-dependent recruitment within the actin cytoskeleton and (3) elucidate
how the mechanosensing by LIM protein LIMD1 initiates the YAP/TAZ
mechanotransduction pathway. These studies have the potential to demonstrate a highly
conserved mechanism of cell mechanosensing, and the methodologies will establish a
novel strategy for tackling cell mechanotransduction.

## Key facts

- **NIH application ID:** 10657771
- **Project number:** 5R01GM143792-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Margaret Lise Gardel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $393,174
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10657771

## Citation

> US National Institutes of Health, RePORTER application 10657771, Mechanisms of Mechanotransduction by LIM Domain Proteins (5R01GM143792-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10657771. Licensed CC0.

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