UC Santa Barbara

Traumatic Brain Injury (TBI) is a leading cause of death and disability worldwide, making it both a global health and economic problem. Despite extensive studies utilizing tissue-level injury models, there is still no effective neural therapeutic available to counteract the neurodegenerative cascade, or secondary injury mechanism, of TBI. In part, this is due to limited understanding of cell-level response to mechanical injury. Prior research has examined the effects of mechanical strain on individual cells, but these studies have involved low strains and low strain rates (ε < 10%, ε ̇ < 100 s-1 ) leaving a largely unexplored injury regime. Furthermore, many of these tools are low throughput (100s of cells per study) which limits the statistical significance of their findings. To more thoroughly explore the effects of cellular injury, a microfluidic and electromagnetically actuated MEMS device (the ‘µHammer’) was developed to apply high strains and high strain rates (ε > 40%, ε ̇ = 200,000 s-1) to individual cells in a high throughput manner (36,000 cells per minute). With this device, compressive strain was applied to human Neural Progenitor Cells (NPCs), which were then monitored for changes in viability and gene expression. Compression studies revealed TBI secondary injury mechanisms (cell death and apoptosis), mechanically sensitive neuroinflammation signaling elements, and a previously unexplored global expression signature. These results suggest that the µHammer device can be an invaluable tool for furthering the understanding of cellular response to mechanical injury.