# Mechanical Regulation of Cell Adhesion by Dynamic Cytoskeletal Assemblies

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2021 · $317,443

## Abstract

Project Summary
Mechanical Regulation of Cell Adhesion by Dynamic Cytoskeletal Assemblies
Epithelial tissue is built by dynamic adhesions, cell-cell junctions, that connect neighboring cells
to maintain tissue cohesion and barrier function yet also allow dynamic processes like wound
healing and tissue morphogenesis. Contractile forces generated within the actomyosin
cytoskeleton are transmitted to cell-cell junctions to control the local cell shape and motions that
sculpt tissue morphogenesis and initiate downstream signaling pathways that control cell fate.
Understanding how the biophysical properties of cell-cell junctions are regulated has widespread
implications for understanding and treating defects during embryonic development, for tissue
engineering and the diagnosis and treatment of metastatic tumors. This proposal leverages
innovative combination of cell biophysics, molecular cell biology, live cell imaging, mathematical
modeling and optogenetics to investigate how RhoA signals regulate contractile forces to drive
changes in cell-cell junction length that control cell shape and, ultimately, tissue morphogenesis.
We propose experiments to elucidate how force-dependent process regulating actomyosin
contractility, membrane remodeling and RhoA signaling feedback to each other to control junction
length and length changes. We approach this problem by integrating molecular cell biology
approaches with advanced quantitative imaging of cytoskeletal dynamics and biophysical
measurements. By obtaining kinetic and kinematic (motion) signatures of proteins at varying
levels of tension, we identify mechanisms of force transmission within focal adhesions and the
actin cytoskeleton. We then collaborate closely with theoretical physicists to test the predictions
of analytical theory and simulations with our quantitative biophysical measurements. This work
builds a biophysical understanding of cell adhesion, tension and shape that, ultimately, will
provide the framework for theories and models of tissue morphogenesis that will have predictive
power in understanding in complex physiological processes. More generally, the strategies
developed in this proposal can be applied more generally to understand how force-sensitive
feedbacks within the cytoskeletal conspire to facilitate cell morphogenic processes. This will
enable the development of improved therapies to treat diseases involved in tissue homeostasis
that currently remain elusive by solely treating molecular targets.

## Key facts

- **NIH application ID:** 10063995
- **Project number:** 5R01GM104032-06
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Margaret Lise Gardel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $317,443
- **Award type:** 5
- **Project period:** 2015-09-21 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063995

## Citation

> US National Institutes of Health, RePORTER application 10063995, Mechanical Regulation of Cell Adhesion by Dynamic Cytoskeletal Assemblies (5R01GM104032-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10063995. Licensed CC0.

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