# Structure and function of stress fibers and cell adhesion sites

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $473,183

## Abstract

Project Summary/Abstract
Multicellular organisms require a high degree of coordination between cells and tissues in order to execute
complex developmental processes and organ functions. This coordination is achieved by communication
mediated by chemical signals such as hormones and growth factors, electrical signals such as action
potentials, and mechanical signals. Mechanical signals can be generated within cells, for example by
regulation of myosin-dependent contractility, or externally, for example by modulation of extracellular matrix
composition. Organs of the respiratory, cardiovascular, and urogenital systems experience mechanical stress
as part of their normal physiological landscape. For the cells within those organs, mechanical force influences
many processes such as cell adhesion, cell motility, cell proliferation, cell survival, stem cell lineage
commitment, and morphogenetic movements during development. A major current challenge in cell biology
is to understand how cells sense and respond to mechanical cues to achieve diverse physiological
responses.
By studying cultured cells, it is possible to study the response of cells to mechanical stimulation delivered in a
controlled fashion. Exposure of fibroblasts to uniaxial cyclic stretch results in a dramatic Stress Fiber-
Remodeling, Repair, and Reinforcement (SF-R3) response. The SF-R3 response is essential for tensional
homeostasis and protects the actin cytoskeleton from force-induced fragmentation. Force-induced changes in
the actin cytoskeleton in turn provide information about the mechanical environment, promoting
mechanosensitive changes in gene expression and other changes in cell behavior. Proteins containing double
zinc fingers, called LIM domains, have recently been shown to play a central role in the response of cells to
mechanical stress. The proposed research will employ a transdisciplinary approach incorporating genetic
manipulations, biochemistry, cell behavioral assays, and quantitative fluorescence imaging to probe the
mechanism by which physical forces result in changes of cell structure and function. The first aim will define
the features of LIM domains that support their ability to recognize actin filaments that are exposed to
mechanical stress. The second aim probes the mechanism by which a MAP-kinase cascade that is activated
by mechanical stress influences effector proteins that are critical for the cellular response to mechanical cues.
The third aim will explore the mechanism by which mechanical cues and the resulting changes in actin
dynamics are communicated to the cell nucleus to affect changes in transcriptional output. The proposed
research will expand our understanding of how mechanical force influences cell physiology and function.

## Key facts

- **NIH application ID:** 9963246
- **Project number:** 5R01GM050877-24
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Mary C. Beckerle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,183
- **Award type:** 5
- **Project period:** 1994-05-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963246

## Citation

> US National Institutes of Health, RePORTER application 9963246, Structure and function of stress fibers and cell adhesion sites (5R01GM050877-24). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9963246. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*