# Epithelial Cell Mechanobiology in Mechanically Heterogeneous Microenvironments

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2020 · $9,882

## Abstract

PROJECT SUMMARY
During development and disease, epithelial cells can migrate collectively, with or without undergoing epithelial-
mesenchymal transition (EMT), through heterogeneous matrices, enabling fundamental processes such as
branching morphogenesis, fibrosis, and tumor invasion. We have shown that extracellular matrix (ECM)
properties beyond the current ECM stiffness, such as confinement and past ECM stiffness, can fundamentally
alter epithelial responses. Through a collection of projects, combining experiments and simulations, this
proposal will reveal new modes collective cell behaviors in matrices of heterogeneous stiffness and
topography. We will measure EMT and migration of epithelial cells around defects in a basement membrane
(BM)-like matrix, determine 3D invasion due to defect-induced EMT, build a computational model to
understand rate-dependent EMT evolution, and pharmacologically disrupt BM degradation. We will also assess
whether the epithelial cells can sense deeply into their matrix and alter responses based on distant stiffening of
the matrix. In another project, we will investigate how cell sheets migrate in 3D-like confined environments of
tunable stiffness and topography. We will connect nuclear shape with cytoskeletal reorganization to understand
how cells adapt to distinct stiffnesses of past and present matrices. Outcomes of these projects will enable new
fundamental understanding of epithelial cell responses to matrix heterogeneities that have remained
unexplored and could reveal novel targets for diseases such as fibrosis and cancer.

## Key facts

- **NIH application ID:** 10111896
- **Project number:** 3R35GM128764-02S2
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Amit Pathak
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $9,882
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111896

## Citation

> US National Institutes of Health, RePORTER application 10111896, Epithelial Cell Mechanobiology in Mechanically Heterogeneous Microenvironments (3R35GM128764-02S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10111896. Licensed CC0.

---

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