# The Mechanical Properties of the Brain and Their Effect on Alzheimer's Disease

> **NIH NIH R03** · JOHNS HOPKINS UNIVERSITY · 2021 · $156,481

## Abstract

Project Summary
Alzheimer's disease (AD) is the most common neurodegenerative disease. However, despite the progress
made in recent years, the causes of AD in most patients are still not well understood. This suggests that new
tools and new perspectives are needed to study AD. It is increasingly recognized that mechanical signals from
cell microenvironment (e.g. matrix stiffness) play important roles in regulating various cell behaviors including
migration, spreading, and differentiation of neural and other stem cells, etc. Recent findings show that the
stiffness (or elastic modulus) of brain changes across the Alzheimer's disease spectrum and it correlates with
disease severity. However, the cellular and molecular mechanisms of how the stiffness of brain may affect AD
are unclear. More importantly, instead of being purely elastic, natural extracellular matrix (ECM) and living
tissues including the brain are viscoelastic, which exhibit stress relaxation over different characteristic time-
scales. The viscoelastic properties of brain with AD are unknown. The overarching goal of this project is to
understand the mechanical properties, particularly the viscoelastic properties, of the brain and their connection
with Alzheimer's disease at the cellular and molecular levels. We have recently developed a biomaterial
system that can recapitulate the viscoelastic behavior of different types of tissues. Using the biomaterials as
tools, we discovered that matrix stress relaxation, in addition to stiffness, is an important mechanical factor
regulating cell–ECM interactions and directing cell activities such as spreading, proliferation, immune
modulation, stem cell differentiation, and tissue regeneration. Microglia maintain cerebral homeostasis and
mediate key functions to support the brain, including controlling the inflammatory response, phagocytic
clearance, and tissue repair. Accumulating evidence suggests that microglia also play an important role in AD
pathology. The hypothesis underlying this project is that healthy brain and the brain affected by Alzheimer's
disease will have different elastic and viscoelastic properties and that altered brain mechanical behavior is a
contributing factor to AD pathology by affecting the activity of microglia. This project has 2 Specific Aims: 1)
Investigate and characterize the elastic and viscoelastic properties of normal and AD affected brain tissues
using mouse models; 2) Develop hydrogels that recapitulate the elastic and viscoelastic properties of healthy
and AD affected brain, respectively, and use the hydrogels as tools to study the effects of matrix stiffness and
viscoelasticity on microglia activity in 3D cell culture. This project uses multidisciplinary approaches to
investigate AD from a direction that has never been explored. Successful completion of the project will have
significant impact in better understanding Alzheimer's disease and open up new research directions in brain
aging and mechanobiology. T...

## Key facts

- **NIH application ID:** 10288723
- **Project number:** 1R03AG073834-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Luo Gu
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $156,481
- **Award type:** 1
- **Project period:** 2021-08-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288723

## Citation

> US National Institutes of Health, RePORTER application 10288723, The Mechanical Properties of the Brain and Their Effect on Alzheimer's Disease (1R03AG073834-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10288723. Licensed CC0.

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