PROJECT SUMMARY The PI’s lab explores the role of mechanical forces in physiological and pathological phenomena. To accomplish this goal, they engineer and probe in vitro models of multi-scale biological systems using bioengineering tools such as microfabricated devices; novel combinations of cells, molecular biology techniques, and cell mechanics tools; and custom quantitative image processing software. They currently use this framework in three main lab focus areas: (1) Exploring the mechanobiology of the vascular endothelium in the context of health, disease, and drug delivery; (2) Probing cell-cell interactions at the blood-brain barrier (BBB) in health and disease; and (3) Understanding basic mechanisms of cell adhesion, migration, and division using engineered cellular microenvironments and model cell systems. Over the next 5 years, the PI’s goal is to establish an NIGMS-MIRA- funded research program that explores critical, outstanding questions about how aquaporins (water channels on the cell membrane) regulate cell migration. The PI’s proposed MIRA research program is motivated by strong phenomonological evidence for the role of aquaporins (AQPs) in cell migration, coupled with a lack of mechanistic links between AQP expression or function and cell behavior, which leaves open critical questions about how AQPs contribute to these physiological phenomena. Hence, the proposed work seeks to explore numerous questions related to fundamental aspects about the regulation of cell migration, with questions centering around whether and how AQPs modulate cell polarization, cell biomechanical properties, migration phenotypes, and response to the microenvironment. The PI’s lab is uniquely positioned to address these outstanding questions using an integrated experimental and theoretical approach, by incorporating our established techniques in cell migration, cell mechanobiology and biomechanics, live cell imaging, molecular biology, microfabrication and microenvironment engineering, and quantitative analysis.