Macrophages Mediate Mesoscale Brain Mechanical Homeostasis

W Woong Young So (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA) B Bailey Johnson (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA) P Patricia B. Gordon (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA) K Kevin S. Bishop (Fischell Department of Bioengineering Maryland Biophysics Program University of Maryland College Park MD 20742 USA) H Hyeyeon Gong (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA) H Hannah A Burr (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA) J Jack Rory Staunton (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA) C Chenchen Handler (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA) K Khanh Loan Ly (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA) R Raman Sood (Fischell Department of Bioengineering Maryland Biophysics Program University of Maryland College Park MD 20742 USA) G Giuliano Scarcelli K Kandice Tanner (Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA)

Abstract

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.

Article Details

Volume / Issue Vol. 38, Issue 6
Published January 01, 2026
ISSN 0935-9648
Publisher Unknown Publisher

Journal Info

Advanced Materials

Unknown Publisher

ISSN: 0935-9648 Physical Sciences

Authors (12)

W

Woong Young So

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

B

Bailey Johnson

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

P

Patricia B. Gordon

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

K

Kevin S. Bishop

Fischell Department of Bioengineering Maryland Biophysics Program University of Maryland College Park MD 20742 USA

H

Hyeyeon Gong

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

H

Hannah A Burr

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

J

Jack Rory Staunton

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

C

Chenchen Handler

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

K

Khanh Loan Ly

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

R

Raman Sood

Fischell Department of Bioengineering Maryland Biophysics Program University of Maryland College Park MD 20742 USA

G

Giuliano Scarcelli

K

Kandice Tanner

Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA