# Mechanical forces regulate leukocyte migration in rapidly deforming tissues

> **NIH NIH F32** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $67,174

## Abstract

Project Summary
Leukocytes must be able to infiltrate and migrate within essentially all tissues of the body in order to deal with
infections and damage that occur throughout the host. Molecular signals like chemoattractants and adhesive
ligands are critical for this process, but immune cells also sense and respond to mechanical cues. While most
tissues of the body are relatively static, the intestines are mechanically dynamic due to the repetitive
contractions of the smooth muscle layers, which apply compressive, stretch, and shear forces to the tissue.
These forces are altered during intestinal infections and chronically dysregulated in inflammatory bowel
disease, pointing towards a relationship between intestinal mechanics and inflammation. Leukocytes are
exquisitely mechanosensitive, but it is presently unknown if they sense or respond to mechanical cues in the
intestines directly. Investigating these forces in rodent models is challenging since the intestinal tissue needs
to be physically immobilized for intravital imaging. Here, we propose to investigate the role intestinal forces
on immune cell function by using the zebrafish system. Intestinal T lymphocytes can be directly visualized in
this system without any surgical manipulation or tissue immobilization. With pharmacological and genetic
tools that interfere with smooth muscle function, we can study intestinal T cell behavior in the presence and
absence of mechanical deformation. In preliminary data, we have found that intestinal T cells migrate by a
distinct strategy in the intestines relative to static tissues like the skin or gills, one characterized by thin,
filopodia-like protrusions that undergo successive branching to propel the T cell forward. Blocking intestinal
movement with smooth muscle inhibitors severely impairs T cell motility within the intestines, but not in static
tissues like the skin. Collectively, these results suggest that mechanical cues dictate T cell migration strategies
in the intestines. This proposal will investigate how T cells sense and respond to deformation in the intestines.
Specifically, we will test the hypothesis that intestinal deformation activates the ion channel Piezo1 to promote
filopodia-like migration. To our knowledge, this will be the first study to investigate how intestinal forces
influence gut immunity and our findings could have broad implications for the diagnosis and treatment of
inflammatory disorders of the gut.

## Key facts

- **NIH application ID:** 10463951
- **Project number:** 1F32GM146398-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Tanner Ford Robertson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463951

## Citation

> US National Institutes of Health, RePORTER application 10463951, Mechanical forces regulate leukocyte migration in rapidly deforming tissues (1F32GM146398-01). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10463951. Licensed CC0.

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