# BIOPHYSICAL CUES SHAPING MACROPHAGE AND T-CELL FUNCTIONS

> **NIH NIH K99** · HARVARD UNIVERSITY · 2024 · $124,967

## Abstract

Project summary. Inflammation underlies majority of human diseases including diabetes, atherosclerosis, and
cancer. These diseases are responsible for majority of deaths and represent substantial global health burden.
Macrophages and T-cells, subsets of immune cells, have emerged as key mediators of inflammation. The role
of biochemical cues in shaping the transcriptional response of these cells have been investigated. However,
accumulating evidence has shown that physical factors also tune their phenotype and effector functions. Recent
two-dimensional studies have shown that mechanical confinement directs the nuclear translocation of
transcription factors in macrophages. Another study found enhanced T-cell killing of cancer cells stiffened
through cholesterol depletion. These studies have contributed to the field of mechano-immunology that seeks to
understand how physical factors direct immune cell fate.
 Recent mechano-immunology findings have laid the groundwork for my proposal aimed at determining
how biophysical cues shape macrophage and T-cell cell behavior. We have developed a three-dimensional
culture that allows us to interrogate how biophysical cues regulate immune cell trafficking and macrophage-T-
cell interaction in the tumor microenvironment. We have already identified that naïve macrophages are more
efficient at trafficking to tumors than polarized macrophages. Furthermore, macrophages adopt different shapes
depending on their activation state and their local microenvironment. Our preliminary results show that T-cells
have longer-lived interactions with rounded macrophages, compared to elongated ones. This implicates
macrophage shape, a biophysical property, in regulating its interaction with T-cells. We will extend these findings
by elucidating the role of matrix viscoelasticity on immune cells behavior and performing a rigorous
immunophenotyping of these cells. In addition, the proposal will implement machine learning algorithms to high
resolution spatiotemporal information obtained from live confocal imaging. This will unlock the potential to identify
heterogenous phenotypic states and quantify their evolution over time. Further, the proposal will integrate
confocal live imaging with the single-cell RNA sequencing data. Such detailed, single cell analysis will identify
genetic programs that are responsible for heterogenous morphometric states.
 The proposed research will be significant because it is expected to yield mechanistic insights that have
broad translational impact for a myriad of diseases where inflammation is the underlying cause. These include
Alzheimer’s, atherosclerosis, arthritis, diabetes, and cancer, which represent a growing global burden. The
pathology of these diseases is orchestrated by macrophages and T-cells. Insight into the mechanobiology of
macrophages, T-cells, and associated intracellular, transcriptional, and epigenetic modifications will deliver novel
therapeutic options. Analysis of morphological h...

## Key facts

- **NIH application ID:** 10881977
- **Project number:** 5K99GM151568-02
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Kolade Adebowale
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $124,967
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881977

## Citation

> US National Institutes of Health, RePORTER application 10881977, BIOPHYSICAL CUES SHAPING MACROPHAGE AND T-CELL FUNCTIONS (5K99GM151568-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10881977. Licensed CC0.

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