Influence of Oxidative Stress on Shear-Induced Mechanotransduction in Red Blood Cells

该奖项的研究目的是回答这样一个问题：氧化应激如何影响红细胞(RBCs)对切应力变化的反应？众所周知，许多化学物质会影响红细胞膜的“流动性”，以及红细胞膜向全身输送氧气的相应能力。然而，关于红细胞对剪切应力变化的动态反应知之甚少，例如动脉粥样硬化性狭窄中存在的粘性应力增加。特别是，氧化应激--与许多疾病状态相关的过多的活性氧物种--被认为会导致红细胞膜僵硬。然而，引人注目的是，目前尚不清楚氧化应激导致红细胞僵化的速度有多快，也不知道剪切诱导的机械转导信号受到影响的速度和程度有多快。根据该奖项进行的研究将结合高速视频和灵敏的光子计数分析来调查红细胞通过模型收缩的行为。如果成功，这些研究将提供第一个关于红细胞在不同量的氧化应激下对剪应力变化的机械和生物反应的硬实验数据。因此，从这些努力中获得的知识将增强该领域在更生理相关的流动条件下模拟和理解RBC行为的能力，最终提供对与氧化应激(例如，糖尿病和肺动脉高压)相关的几种疾病状态的更基本的了解。该教育计划的重点是利用获奖者在小学一级的高速视频方面的专业知识，与当地的一家儿童科学博物馆合作，开发互动的动手展览。在本科生层面，这项研究的结果将被纳入一个名为“血液机制”的研讨会，该研讨会将专注于让学生接触到校园内的研究机会，并帮助吸引犹豫不决的一年级学生进入科学或工程领域。

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.