# Mechanisms of mechanosensing through integrins

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $412,050

## Abstract

Project Summary
 Cells sense extracellular matrix (ECM) stiffness and physical forces applied through the
ECM through integrin-mediated adhesions. These mechanotransduction processes play critical
roles in embryonic development, normal physiology and multiple diseases, including cancer,
hypertension, atherosclerosis and fibrosis among others. However, mechanical responses differ
between cell types, between the same cell type in different states, and even in different regions
of single cells. While much has been learned about mechanotransduction through integrins, a
major area of ignorance is how different types and components of matrix adhesions modulate
cell responses to force. The aim of this project is therefore to characterize the mechanosensing
properties of distinct types and compositions of integrin mediated adhesions and elucidate the
molecular basis for these differences.
 A major limitation in our current understanding of mechanosensing by different types of
adhesions is that current, morphology-based classifications into nascent, focal or fibrillary
adhesions or focal complexes are imprecise, with little information about composition or
structure. Additionally, adhesions in cells continuously evolve, so that actual adhesions are
often mixtures of different types. Recent work has now defined specific molecular complexes
that serve as modules for construction of different adhesion classes. Indeed, the data argue that
adhesions have a modular structure with these protein complexes serving as the core modules
that are combined and modified to generate diversity. Based on this hypothesis, we will:
1.Combine biochemical approaches with novel imaging and machine learning methods to
elucidate the composition and behaviors of the distinct adhesion modules. 2.Utilize these
biochemical and imaging methods in conjunction with assays of cytoskeletal and adhesion
dynamics and tension to characterize the cytoskeletal organization and dynamics for the distinct
adhesion complexes. 3.Combine novel imaging and engineering approaches to characterize
the distinct signaling properties of the different adhesion states and their responses to substrate
stiffness and applied strain.

## Key facts

- **NIH application ID:** 9933958
- **Project number:** 5R01GM047214-28
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Martin A Schwartz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,050
- **Award type:** 5
- **Project period:** 1991-06-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933958

## Citation

> US National Institutes of Health, RePORTER application 9933958, Mechanisms of mechanosensing through integrins (5R01GM047214-28). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9933958. Licensed CC0.

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