CAREER: Biomechanics of Red Blood Cell Adhesion and Deformability

健康的红细胞是柔软的，没有粘性，因此它们可以很容易地穿过身体血管的最西边。红细胞的硬度和粘性增加会损害血液循环，这确实发生在许多疾病和病症中，包括贫血、败血症、疟疾、狼疮、重金属中毒、输血并发症、糖尿病、癌症、肾脏和心血管疾病、肥胖症和一些神经系统疾病。医学对红细胞在这些条件下的机械变化没有完全的了解。 这个教师早期职业发展（CAREER）项目将推进我们对红细胞粘附和变形性的微循环知识，使用特殊构建的微通道设备，具有可调节的粘性，人们可以看到细胞的变形，因为它们流动，变形和与微血管壁相互作用。首席研究员将利用这些实验中产生的美丽图像和科学艺术，通过与克利夫兰艺术学院合作开发的科学、技术和艺术（STArt）教育计划接触社区。STArt计划旨在通过动手，该CAREER奖的研究目标是验证红细胞的粘附亲和力是其变形性和磷脂酰丝氨酸转运到外膜表面的功能的假设。红细胞的特殊变形性是由其膜骨架促进的，其与粘附受体物理连接。磷脂酰丝氨酸是位于细胞膜内叶的磷脂。尽管磷脂酰丝氨酸外膜表面的易位与粘附相关，但其在红细胞粘附亲和力增加中的作用仍不清楚。该研究将在单细胞水平上系统地研究活红细胞在微生理血流中的生物力学特性。获得的新知识将回答重要的问题：（1）哪些红细胞受体与较高的粘附亲和力和较低的变形性相关？(2)粘附亲和力是红细胞变形性、磷脂酰丝氨酸移位和功能的替代指标吗？(3)是否可以仅根据其粘附亲和力和变形性降低来识别不健康的红细胞并将其从循环中排除？拟议的研究将开创一个综合了解红细胞粘附和变形能力，这可能是相关的任何疾病伴随着微循环障碍。

Healthy red blood cells are soft and are not sticky so that they can slip easily through even the narrowest of blood vessels in the body. Increased stiffness and stickiness of red blood cells can impair blood circulation and this does occur in many diseases and conditions, including anemias, sepsis, malaria, lupus, heavy metal poisoning, blood transfusion complications, diabetes, cancer, kidney and cardiovascular diseases, obesity, and some neurological disorders. Medicine does not have a complete understanding of the mechanical changes of red blood cells in these conditions. This Faculty Early Career Development (CAREER) project will advance our knowledge of red blood cell adhesion and deformability in the microcirculation using special built micro-channel devices that have adjustable stickiness where one can see the deformation of the cells as they flow, deform and interact with the micro-vessel walls. The principal investigator will use the beautiful imagery and the scientific art that arises from these experiments to reach out to the community through the Science, Technology and Art (STArt) education program that will be developed in collaboration with the Cleveland Institute of Art. The STArt program aims to stimulate scientific curiosity and interest in high school students through hands-on, scientific art themed workshops.The research objective of this CAREER award is to test the hypothesis that a red blood cell's adhesion affinity is a function of its deformability and phosphatidylserine translocation to the outer membrane surface. The exceptional deformability of the red blood cell is facilitated by its membrane skeleton, which is physically connected to the adhesion receptors. Phosphatidylserine is a phospholipid located on the inner leaflet of the cell membrane. Even though the translocation of phosphatidylserine to the outer membrane surface has been correlated to adhesion, its role in red blood cell's increased adhesion affinity remains unclear. The research will systematically investigate, at the single cell level, the biomechanical properties of live red blood cells in microphysiological blood flow. The new knowledge gained will answer important questions: (1) which of the red blood cell receptors are associated with higher adhesion affinity and lower deformability? (2) Is the adhesion affinity a surrogate measure of red blood cell's deformability, phosphatidylserine translocation, and function? (3) Can the unhealthy red blood cells be identified and excluded from the circulation solely based on their adhesion affinity and reduced deformability? Proposed research will pioneer an integrated understanding of red blood cell adhesion and deformability, which may be pertinent to any disease accompanied by microcirculatory impairment.