# Mechanotransduction in Multicellular Systems

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $304,924

## Abstract

PROJECT SUMMARY
Tissue structure alterations are primary determinants of many developmental, physiological, and
pathophysiological processes and often involve the coordinated movements of groups of physically interacting
cells, a phenomenon referred to as collective cell migration. This phenomenon takes many different forms in a
variety of processes such as embryonic development, wound healing, and cancer metastasis. Understanding
the determinants and regulators of collective cell migration is therefore of great importance to human health.
The critical processes mediating collective cell migration are thought to involve force generation and
mechanical coupling among cells, but the underlying molecular mechanisms remain poorly understood. The
long-term goal of this work is to understand the key mechanically-sensitive mechanisms mediating collective
cell migration. Toward this goal, we have created and validated a set of innovative techniques for studying
molecular scale, mechanically-sensitive processes within collectively migrating cells. Specifically, we focus on
the mechanical linker protein vinculin, given its ability to regulate force-induced adhesion strengthening,
established role in the development of load-bearing tissues, and emerging function as a mechanically-sensitive
regulator of tumor progression. The overall objective of this proposal is to use these techniques to develop and
test a novel conceptual model of collective cell migration in which forces generated by a leader cell activate
vinculin-associated mechanosensitive pathways in surrounding cells to initiate coordinated directional
migration. We will determine if 1) collectively migrating cells generate spatial gradients of molecular tension
across vinculin, 2) spatial variations in force lead to the differential activation of mechanically sensitive
signaling, 3) the relationship between vinculin load and vinculin dynamics is spatially organized and
biochemically regulated during collective cell migration, and 4) cellular adhesion structure stability determines
the form of collective cell migration. An enhanced mechanistic understanding of these processes would
increase our fundamental knowledge of the regulation of tissue structure. Thus, these studies are relevant to
the NIH's mission, as they will lead to new insights in many fields including cancer, birth defects, wound
healing, and tissue regeneration.

## Key facts

- **NIH application ID:** 9842295
- **Project number:** 5R01GM121739-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Brenton D Hoffman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $304,924
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842295

## Citation

> US National Institutes of Health, RePORTER application 9842295, Mechanotransduction in Multicellular Systems (5R01GM121739-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842295. Licensed CC0.

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