Nanomechanics of Erythrocyte Adhesion

红细胞粘附的纳米力学

• 批准号: 1235025
• 负责人: Georgios Lykotrafitis
• 金额: $ 40万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1235025&HistoricalAwards=false
• 关键词: Nanomechanics; Erythrocyte; Adhesion

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.

该奖项的研究目标是在单分子水平上表征红细胞粘附受体及其相应配体之间的相互作用，并测量激动剂激活信号对粘附事件强度和频率的影响。这些发现将与流动条件下完整红细胞与粘附配体的离体粘附相关。传统上，红细胞被认为是含有血红蛋白的惰性细胞，仅作为氧载体发挥作用。最近，已经发现红细胞在其表面上表达出乎意料数量的粘附受体，并且我们开始理解外部刺激，例如肾上腺素能激素，甚至增加成熟红细胞的粘附能力。原子力显微镜结合微流控技术将被用来进行测量，而多尺度数值模拟将被用来关联单分子实验结果与整体RBC粘附experiments.The拟议的研究将回答非常基本的问题，红细胞粘附。预计将确定哪些RBC受体与粘附事件的强度更高和频率增加有关，以及外部信号如何在分子水平和生理血流条件下改变RBC粘附。这些结果有望产生非常重要的积极影响，因为所鉴定的粘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学靶点和治疗方法。该教育计划将导致在康州大学斯托尔斯开发一系列关于细胞力学的跨学科研究生课程。它还将促进高中教师和学生的工程和科学。特别是，它将促进当地一所高中的9至11年级女生参与科学和技术。