Nanomechanics of Erythrocyte Adhesion

该奖项的研究目的是在单分子水平上表征红细胞黏附受体与其相应配体之间的相互作用，并测量激动剂激活信号对黏附事件强度和频率的影响。这一发现将与流动条件下完整红细胞与黏附配体的体外黏附相关。传统上，红细胞被认为是含有血红蛋白的惰性细胞，只起到氧气载体的作用。最近，人们发现红细胞表面表达了数量意想不到的黏附受体，我们开始了解到外部刺激，如肾上腺素能激素，可以增加即使是成熟红细胞的黏附能力。原子力显微镜和微流控相结合将被用来进行测量，而多尺度数值模拟将被用来将单分子实验结果与整体红细胞黏附实验相关联。拟议的研究将回答与红细胞黏附相关的非常基本的问题。人们希望确定哪些RBC受体与更高强度和更高频率的黏附事件有关，以及外部信号如何在分子水平和生理血流条件下改变RBC黏附。这一结果有望产生非常重要的积极影响，因为已识别的黏附受体和机制很可能为周围血管疾病的预防和治疗提供新的药理靶点和治疗方法。该教育计划将导致在斯托尔斯的康涅狄格州大学开发一系列跨学科的细胞力学研究生课程。它还将在高中教师和学生中推广工程和科学。特别是，它将促进9至11年级女孩参加当地一所高中的科学技术课程。

The research objective of this award is to characterize at the single molecule level the interactions between erythrocyte adhesion receptors and their corresponding ligands, and to measure the effect of agonist activation signaling on the strength and the frequency of adhesion events. The findings will be correlated with ex vivo adhesion of intact erythrocytes to adhesive ligands under conditions of flow. Traditionally, erythrocytes were considered to be inert cells containing hemoglobin and functioning only as oxygen carriers. Recently, it has been found that erythrocytes express an unexpected number of adhesion receptors on their surfaces and we begin to understand that external stimuli, such as adrenergic hormones, increase the ability of even mature erythrocytes to adhere. Atomic force microscopy combined with microfluidics will be used to carry out the measurements while multiscale numerical simulations will be employed to correlate single molecule experimental results with overall RBC adhesion experiments.The proposed research will answer very fundamental questions related to erythrocyte adhesion. It is expected to identify which of the RBC receptors are related to higher strength and increased frequency of adhesion events and how external signaling modifies RBC adhesion at the molecular level and in physiological blood flow conditions. The results are expected to have a very important positive impact because the identified adhesion receptors and mechanisms are very likely to provide new pharmacological targets and therapeutic approaches for the prevention and treatment of peripheral vascular diseases. The educational plan will result in the development of a series of interdisciplinary graduate courses on Cell Mechanics at UConn, Storrs. It will also promote engineering and science in high school teachers and students. In particular, it will advance the participation of 9th to 11th grade girls from a local high school in science and technology.