# Macrophage-Fibroblast Communication in Cell Migration and Extracellular Matrix Remodeling

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $388,945

## Abstract

Project Summary
Cell-cell signaling maintains homeostatic functions in the presence of a dynamic environment that involves cell-
derived paracrine factors, mechanical cues, and varying oxygen levels. Macrophages and fibroblasts are key
cell types present in almost all mammalian tissues that integrate diverse signals from their environment and are
involved in tissue homeostasis. Existing experimental models have not been able to precisely control cell-derived
factors and oxygen levels while simultaneously monitoring cell migration and cell-cell communication at the
single cell level in the extracellular matrix (ECM). Hence, a critical knowledge gap exists in understanding the
fundamental mechanisms that control intercellular signaling in complex microenvironments. My research group
will address this knowledge gap by investigating two key questions: (1) How is macrophage migration regulated
by the interplay between fibroblast-secreted paracrine and mechanical cues in a 3D environment? (2) How do
low oxygen levels modulate fibroblast activation, ECM remodeling, and macrophage-fibroblast crosstalk? To
address the first question, we will integrate intracellular signaling biosensors with a novel microfluidic technology
to control paracrine factors and cell-generated forces precisely. Results from these studies will uncover
fundamental principles of cell migration. To address the second question, we will engineer multi-layer microfluidic
devices with integrated imaging-based multiplexed analysis of fibroblast activation and measurement of
mechanical forces. Results from the second question will provide mechanistic insights into the physiological
process of multicellular oxygen-sensing and ECM remodeling. Our past studies and preliminary results using 3D
microfluidic devices demonstrate the feasibility of engineering tissue microenvironments and controlling cellular
responses in real-time. In summary, the proposed studies will establish a new microfluidics-based approach to
studying basic mechanisms of cell migration and ECM remodeling in tissue microenvironments with
spatiotemporally defined oxygen landscapes, mechanical forces, and paracrine factors.

## Key facts

- **NIH application ID:** 10911999
- **Project number:** 5R35GM150815-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ioannis Zervantonakis
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,945
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911999

## Citation

> US National Institutes of Health, RePORTER application 10911999, Macrophage-Fibroblast Communication in Cell Migration and Extracellular Matrix Remodeling (5R35GM150815-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10911999. Licensed CC0.

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