(680e) Surface Compliance Induced Reactive Astrocytes: An in Vitro Model of Astrogliosis

Studies have shown that the brain, a soft tissue highly susceptible to injury, can increase in stiffness as a result of injury and disease such as stroke, traumatic brain injury and cancer. The most abundant non-neuronal cell type in the brain, astrocytes, perform a number of support roles for healthy neuronal function including ion homeostasis, extracellular matrix manipulation and neurotransmitter recycling. Astrocytes have been observed to respond to brain injury and disease by reverting to an activated phenotype resulting in astrogliosis. This state has potential toward the restoration of healthy brain function or injury progression based on the molecular phenotype initiated by the injury or disease. The activated astrocyte phenotype has been studied under numerous chemical cues however the phenotype resulting from mechanical cues, such as the change in tissue stiffness observed in the event of traumatic brain injury, tumor progression and stroke, is not well documented. Therefore the aim of this study is to utilize polydimethylsiloxane (PDMS) substrates of biologically relevant compliance to study the molecular mechanisms initiating and sustaining the reactive astrocyte phenotype resulting from an increase in surface mechanical stiffness in vitro. Our model successfully induces the astroglial phenotype affirmed by change in cell morphology, increased cell proliferation and increased glial fibrillary acidic protein (GFAP) expression. Furthermore, we observed a surface compliance dependent increase in stress and a decrease in cellular function. This model has the potential for characterization of astrogliosis induced by tissue stiffness which may be utilized in development of therapeutics for brain injury and disease.