# Macrophages Mediate Mesoscale Brain Mechanical Homeostasis

## TL;DR

This study shows that microglia, the brain's immune cells, actively maintain tissue mechanics and influence brain structure through immune-driven remodeling.

## Contribution

The study introduces a novel framework linking immune activity with brain mechanical homeostasis using advanced imaging techniques.

## Key findings

- Microglia actively sustain tissue viscoelasticity rather than being quiescent.
- CSF1R-driven stromal remodeling alters brain mechanical properties in vivo.
- Immune activity is directly linked to viscoelastic integrity and neural tissue plasticity.

## Abstract

Mechanical cues orchestrate cellular behavior in the brain, yet how they interface with immune regulation remains unresolved. Here, gigahertz‐frequency Brillouin microscopy with optical trap‐based active microrheology is integrated to map the mechanical impact of macrophage activity across timescales. It is revealed that microglia, brain's resident macrophages, actively sustain tissue viscoelasticity, rather than quiescently residing within the tissues under normal conditions. Moreover, macrophage colony‐stimulating factor 1 receptor (csf1r)‐driven stromal remodeling alters brain mechanical properties in vivo. These findings establish a direct link between immune activity, viscoelastic integrity, and structural plasticity of neural tissue. By bridging high‐frequency material responses with immune‐driven remodeling, the approach provides a framework for decoding how biophysical properties regulate slower‐timescale signaling and offers mechanistic insights for increasing the efficacy of csf1r‐targeted therapies in cancer and neurodegeneration.

We investigated the role of infiltrating immune cells in sculpting the developing brain. Using Brillouin microscopy and active microrheology, we found microglia actively maintain tissue viscoelasticity. Moreover, colony stimulating factor one receptor (CSF1R)‐driven stromal remodeling alters brain mechanics in vivo. These findings link immune activity, viscoelastic integrity, and neural tissue plasticity, offering insights for CSF1R‐targeted therapies in cancer and neurodegeneration.