The research objective of this award is to answer the question: how does oxidative stress affect the response of red blood cells (RBCs) to changes in shear stress? Many chemical species are known to affect the "fluidity" of red blood cell membranes and their corresponding ability to deliver oxygen throughout the body. Little is known, however, about the dynamic response of RBCs to changes in shear stress, such as the increased viscous stress present in an atherosclerotic constriction. In particular, oxidative stress - the excess in reactive oxygen species associated with many disease states - is known to cause RBC membranes to rigidify. Strikingly, however, it is unknown how quickly oxidative stress causes RBCs to rigidify, and it is unknown how quickly or to what degree shear-induced mechanotransductive signaling is affected. Studies conducted under this award will combine high-speed video and sensitive photon-counting assays to investigate the behavior of RBCs moving through model constrictions.
If successful, these studies will provide the first hard experimental data regarding the mechanical and biological responses of RBCs to changes in shear stress under varied amounts of oxidative stress. The knowledge gained from these efforts will thus enhance the field's ability to model and understand RBC behavior under more physiologically relevant flow conditions, ultimately providing a more fundamental understanding of several disease states associated with oxidative stress (e.g., diabetes and pulmonary hypertension). The educational plan focuses on leveraging the awardee's expertise in high-speed video at the elementary school level, by collaborating with a local children's science museum to develop interactive hands-on exhibitions. At the undergraduate level, the results of this research will be incorporated into a seminar titled "The Mechanics of Blood," which will focus on exposing students to research opportunities across campus and helping attract undecided first-year students to science or engineering.
