Brain microglial motility modulated by substrate stiffness

Abstract

The immune cells play a crucial role in maintaining homeostasis within tissues, constantly monitoring the surrounding environment and responding to external changes. Microglia, the immune cells in the brain, undergo changes in shape and increased motility when activated by external stimuli. This suggests the significance of the motility of microglia in the brain's immune response. Recent research has revealed that the stiffness of the brain varies depending on the region, aging process, and the progression of neurodegenerative diseases such as Alzheimer's. Therefore, this study aims to gain deeper insights into the brain's immune response by investigating how changes in brain stiffness affect the motility of microglia. Firstly, we propose a method using both phase-contrast microscopy and differential interference contrast microscopy to simultaneously decompose the motility and shape changes of microglia. This allows for accurate measurement of both the motility and shape changes of microglia. Through this, we confirmed the effect of the brain substrate stiffness on the motility of microglia. The results revealed differences in the diffusivity, directional switching tendency, and traction force of microglia depending on changes in brain substrate stiffness. These findings indicate that the stiffness of the brain plays a crucial role in the motility of microglia, and the resulting changes in the physical motility characteristics of microglia have the potential for use as a biomarker for the brain's immune response.