Development of a Microfluidic Platform to Study Effects of Physical Stresses on Microglial Activation

Abstract

Brain cells are surrounded by bodily fluids such as cerebral interstitial and cerebrospinal fluid and exposed to continuous electrical stimulations. These physical microenvironments are known to play an important role in the mechanical protection of the brain cells and regulation of their functions in both physiological and pathological states. Among many cell types, microglia cells sensitively respond to the changes in physical stimuli and are transformed into different activation states featuring distinct morphological and migration patterns. To study microglial activation in a brain-like environment, we developed a microfluidic channel to realize physiologically relevant physicochemical microenvironments of controlled interstitial flow, electric field, and chemical gradients. Under various shear stress conditions, bipolar cells are transformed into an amoeboidal cells with enhanced spreading movement. Similarly, electric field promotes transformation of microglial phenotype with enhanced migration as well as phagocytic activity. Since the change in the activation state of microglia is closely related to neurodegenerative diseases, this work might provide unconventional perspectives for pathological outbreaks in the brain.Acknowledgement: This research was supported by the fundamental research project (A0601003001) and high risk high return project (N10140037) funded by KAIST.