# Dissecting the mechanism of cell migration at the systems level

> **NIH NIH R35** · CARNEGIE-MELLON UNIVERSITY · 2020 · $275,685

## Abstract

Project Summary/Abstract
Cell migration is required for many important physiological and pathological processes such as embryonic
development, wound healing, and cancerous invasion. As a process that involves concerted action of multiple
ensembles of molecules over the length of the entire cell, cell migration cannot be understood using
conventional molecular approaches alone without considering sensing, actuation, and control at the whole cell
level. This project seeks to approach migrating cells in a top-down manner as an integrated mechanochemical
system. Based on observations that likely represent the manifestation of a complex network of molecular
interactions, we may deduct how the underlying machine operates. The project will be facilitated by the
development of new technologies, including 3D printing of polyacrylamide hydrogels and machine learning for
cell tracking, traction force microscopy, and super resolution imaging. We will address three important aspects.
First, we will ask how cells initiate migration through a process known as symmetry breaking, which causes a
symmetrically spreading cell to initiate directional migration. We will examine various anisotropic properties of
the substrate as potential symmetry breaking cues. In addition, the function of filopodia as possible sensors for
symmetry breaking will be studied with imaging and pharmacological approaches. Second, we will address
several poorly understood aspects of 2D and 3D cell migration. By following migrating cells over a long distance
at a high magnification, we expect to place the newly discovered process of contact following in the context of
cell collectives. To understand how cell shape control, cell-cell interaction, and cell migration respond to 3D
environment, we will use 3D printed polyacrylamide to create model systems and systematically vary
geometrical and mechanical parameters. We will then extend the experiments to decellularized lung scaffolds,
which have been used for tissue engineering, to determine how migration characteristics in 3D is related to the
promotion of tissue formation. Another overlooked area we will examine is the function of the tail in defining
cell polarity and mediating contact following. Third, we will seek mechanistic understanding of cellular
responses to cyclic stretching, which occurs in various tissues. A novel imaging approach will allow us to
determine the responses during the stretching and relaxation phase respectively. A combination of
experimentation and computer modeling is planned to explain why epithelial cells respond to static stretching
along the direction of forces but perpendicularly in response to cyclic stretching. We will also test the
hypothesis that responses to cyclic stretching can cause cell intercalation, a fundamentally important process in
embryonic morphogenesis. We expect our results to complement studies at the molecular level and bring
paradigm shifting insights into cell migration for both basic ce...

## Key facts

- **NIH application ID:** 9931843
- **Project number:** 1R35GM136345-01
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** Yu-li Wang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $275,685
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931843

## Citation

> US National Institutes of Health, RePORTER application 9931843, Dissecting the mechanism of cell migration at the systems level (1R35GM136345-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9931843. Licensed CC0.

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