The Effect of Fluidic Shear Stress on Mitochondrial Networks in Endothelial Cells

Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives yearly. Among CVDs, Coronary Artery Disease (CAD) develops from the accumulation of plaque in coronary arteries from atherosclerosis. This disrupts blood flow and increases the risk of heart-related complications. Blood flow within blood vessels is maintained by mechanical forces like shear stresses. Atheroprotective fluid shear stresses, between 1-10 dyne/cm2, are known to promote vessel homeostasis while atheroprone fluid shear stresses, above 10 dyne/cm2, disrupt the vasculature metabolic processes. Endothelial cells (ECs) line up the lumen of blood vessels and are exposed to mechanical forces. ECs regulate vascular function and blood vessel health by a process called mechanotransduction, which converts mechanical stimuli into biochemical signals. Mitochondrial network dynamics (MNDs) refer to the dynamic processes of fission and fusion influencing the morphology and functions of mitochondria. MNDs within ECs are known to be influenced by fluidic shear stress. However, the intricate relationship between fluidic shear stresses and mitochondria within ECs is still being studied. We hypothesize that atheroprone fluid shear stress will inhibit the homeostasis of ECs by hyper-fusion or hyper-fission of MNDs. In this project, we aim to image live cells using an innovative approach of holotomographic microscopy with the fabrication of a microfluidic chip to better understand the impact of fluid shear stresses on MNDs within ECs. Overall, this project participates in deepening our understanding of the cardiovascular system while proposing new openings for mitochondria-targeted innovations in the context of CVDs.