Pairing Finite Element Modeling with 3D Strain Measurements for Mechanotransduction Measurements 

Approximately 5.5 million people suffer from Alzheimer’s Disease (AD) in the United States, which can cost up to $290 billion in total costs. Surprisingly, 40-50% of patients that are diagnosed with AD also present clinical signs of vascular origins with no clear understanding as to why this occurs. Recent evidence seems to suggest that both high blood pressure and fluid shear stress are two potential factors that could influence progression of AD by influencing the mechanotransduction events at the brain microvasculature. The endothelium is well documented to play a major role in sensing changes in mechanical forces and respond accordingly to maintain homeostatic conditions. However, pathological levels of circumferential and wall shear stress can lead to impaired endothelial barrier function and inflammation under both static and pulsatile flow conditions. Additionally, high levels of blood pressure can exert compressive strains on the surrounding tissue, which are thought to impact surrounding cells such as neurons in the brain. To better understand the mechanisms of how endothelial and neuronal function is impacted during these conditions, we are developing a 3D microfluidic in vitro blood-brain barrier model that can simultaneously change in fluid shear stress and pressure. Using the in vitro model, we aim to measure 3D deformations due to the applied loading (i.e. shear and pressure) by introducing fluorescent microbeads in the surrounding matrix and tracking them over time. To characterize the mechanical response, we will couple the in vitro model with a finite element model to calculate the induced stresses and strains.