# Dissecting mechanisms of collective migration

> **NIH NIH R35** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $361,054

## Abstract

PROJECT SUMMARY
Background: Collective migration is a type of cell migrationwhere groups of cells move together in a coordinated
fashion that is essential for development and disease progression, including wound healing or metastasis. During
collective migration, a few cells at the front (i.e. leader cells) define the leading edge, integrate signals from the
surrounding environment and send signals to neighboring (follower) cells. Recent findings in our lab demonstrate in
order for collective migration to occur, leader cells must first arrive (or polarize) at the front edge to begin the
collective migration cascade. However, it is largely unknown how leader cells interpret signals from the
microenvironment via sensing of mechanical forces and how cell junction forces contribute to leader cell activation
and collective migration. Thus, there is much interest to understand leader cell mechanotransduction and the
signaling mechanisms used to drive collective migration.
Hypothesis: Our central hypothesis is that dynamic extracellular matrix cues activate leader cell mechanics
via both cell-matrix and cell-cell contacts, are required to initiate and sustain directional collective migration.
Goals: This project is divided into 3 main goals: 1. Investigate the effect of biomechanical cues to activate
leader cells and directional collective migration 2. Elucidate which and how leader cell mechanics are
responsible for leader cell development, and 3. Investigate the functional role of forces at cell contacts and how
cell junctional forces contribute to collective migration
Study Design: We will combine microfluidic lab-on-a-chip devices which can modulate multiple
microenvironment features, and investigate how mechanical cues effect leader cell development and
directional collective migration. We will also incorporate FRET-based tension sensors to our microfluidic
platform so we can quantify changes in cell-cell load during leader cell driven collective migration in real-time.
To understand how cell-matrix interactions effect leader cell development, we will measure matrix deformation
rate as exerted by leader cells on the surrounding environment. Furthermore, we will perform series of targeted
knockdowns and rescue experiments to investigate our ability to disrupt, prevent, or revive collective migration
by disrupting leader cell signaling. These studies will reveal how microenvironment cues, cell-matrix, and cell-
cell interactions contribute to leader cell development and mechanics that is essential for collective migration.
Impact: Understanding the development of collective migration, and the role of leader cells in driving collective
migration will pave the way for accelerated understanding of biological processes where collective migration is
fundamental to its success.

## Key facts

- **NIH application ID:** 10941082
- **Project number:** 1R35GM155045-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Priscilla Y Hwang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $361,054
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941082

## Citation

> US National Institutes of Health, RePORTER application 10941082, Dissecting mechanisms of collective migration (1R35GM155045-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10941082. Licensed CC0.

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