Role of PIEZO1 in mediating phosphatidylserine (PS) exposure on red blood cells (RBCs) in patients with Sickle Cell Disease (SCD)

This project aims to elucidate the role of the mechanosensitive ion channel PIEZO1 in regulating phosphatidylserine (PS) exposure on red blood cells (RBCs) among patients with Sickle Cell Disease (SCD). SCD, a genetic disorder, results in RBC deformation that precipitates severe vaso-occlusive crises and subsequent organ damage. By employing high-throughput electrophysiology via the Automated Patch Clamp (APC) system alongside physiological flow simulations using the ibidi pump system, the study aims to quantify PIEZO1 activity in sickle RBCs. Research efforts will extend to examining mechanotransduction changes under variable solution application speeds and oxygen deprivation. Further investigations will assess the influence of cytoskeletal modifications on PIEZO1 function. Finally, a pivotal aspect of the study involves correlating PIEZO1 activity with RBC phenotypic traits, such as PS exposure and cellular adhesion to endothelial linings. Through this comprehensive methodology, the project intends to uncover the pivotal contributions of PIEZO1 to SCD pathophysiology and to identify potential therapeutic targets that could alleviate disease manifestations. Integrating cutting-edge electrophysiological techniques with precise simulations of physiological conditions, the research is poised to offer profound insights into the biophysical characteristics of PIEZO1 and its consequential effects on RBC dynamics in SCD.