# Molecular Determinants of Confined Migration

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $291,527

## Abstract

Project Summary: In numerous processes including development and metastasis, cells can move in
microtracks within the 3D microenvironment. These microtracks are formed by cells themselves through the use
of matrix metalloproteinases that degrade matrix, or microtracks can exist as a product of the natural architecture
of organs. While microtrack migration occurs in vivo, little is known about the specific mechanisms that cells
employ to move in microtracks. We have developed a unique platform using microfabrication to recreate these
microtracks in vitro by micromolding collagen. Microtracks can be made in various sizes, and they can be
patterned into multiple different shapes including tapered channels and bifurcated channels. Our microfabricated
microtracks are structurally indistinguishable from tracks found in vitro and in vivo. Moreover, they offer a distinct
advantage over other PDMS-based platforms because the collagen is amenable to cell adhesion on all 4 walls
of the track, the fibrous walls of the microtrack can be deformed by cells, and the tracks more closely mimic the
mechanical and chemical properties found in vivo. Importantly, our work to-date has shown that the mechanisms
driving movement in microtracks are not the same as those mediating cell migration on 2D substrates or in
unmolded collagen. Here, we propose to build upon two of our major prior findings, which are that: 1. Vinculin
is required for microtrack movement, 2. Cellular confinement alters migration and correlates with cell metabolism.
Using this novel microtrack platform in concert with engineered probes to monitor adhesion and cellular energy,
optogenetic probes to alter cell contractility and cellular protrusions, and novel force measurement techniques,
we will investigate the molecular mechanisms driving cell migration and decision-making during migration in
microtracks with a focus on adhesion dynamics and cellular energetics. In Aim 1, we investigate the role of focal
adhesion dynamics and tension, focusing on vinculin-talin-actin interactions based on our preliminary showing
vinculin mediates unidirectional motion. We will investigate the linkage between vinculin, talin and actin, and we
will probe the force transmission occurring at the sites of cell-matrix adhesion. In Aim 2, we will investigate how
cellular energetics and the availability of nutrients affects migration and migration decisions in confined spaces.
Based on our prior work indicating that the extracellular matrix structure alters ATP utilization, we hypothesize
that increased confinement will increase the energetic needs of the cell. In Aim 3, we will investigate the
molecular and mechanical mechanisms governing cell migration decisions. Constructs designed to disrupt force
transmission between the cell and the matrix and pharmacological interventions will be used to assess the effects
of cell contractility and cell stiffness on cellular energy utilization, adhesion, and migration direction decis...

## Key facts

- **NIH application ID:** 9876944
- **Project number:** 5R01GM131178-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Cynthia A. Reinhart-King
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $291,527
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876944

## Citation

> US National Institutes of Health, RePORTER application 9876944, Molecular Determinants of Confined Migration (5R01GM131178-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9876944. Licensed CC0.

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