# Mechanical Self-Assembly of Dense Fibrotic Tumor Microenvironments: Mechanisms and Therapy

> **NIH NIH R21** · YALE UNIVERSITY · 2020 · $183,056

## Abstract

Project Summary
Densified fibrotic environments are commonly observed in aggressive solid tumors. The mechanisms and
origins of these environments are not well understood despite their clinical relevance. Here, we take an
integrated computational and experimental approach to decipher the mechanical mechanisms that lead to
plastic, irreversible extracellular matrix (ECM) densification in the vicinity of tumors. We emphasize on the
impact of dynamic cellular events, particularly dynamic local force generation, on ECM fiber kinetics that leads
to spatiotemporal remodeling of the ECM network. We will perform high resolution time lapse imaging to
quantitatively capture the force-induced densification of the ECM near tumor clusters, and we will perform
computational simulations of dynamic 3D ECM networks to uncover mechanistic insights that govern this
phenomenon. Finally, quantitatively guided by our computational and experimental findings, we will develop a
novel drug delivery strategy that selectively targets the dynamic mechanical landscape of the tumor
microenvironment.

## Key facts

- **NIH application ID:** 9948675
- **Project number:** 5R21EB026630-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael MAK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $183,056
- **Award type:** 5
- **Project period:** 2018-09-06 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948675

## Citation

> US National Institutes of Health, RePORTER application 9948675, Mechanical Self-Assembly of Dense Fibrotic Tumor Microenvironments: Mechanisms and Therapy (5R21EB026630-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9948675. Licensed CC0.

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