Deformability distributions in heterogeneous red blood cell populations

描述（由申请人提供）：红细胞在循环中变形和承受高剪切应力的独特能力随着膜中分子相互作用的改变或细胞质溶胶的改变而丧失。我们已经开发了一种新的技术“单细胞微室阵列”或SiCMA，以快速分析异质细胞群，并计划证明该技术将允许在异质红细胞群体中变形和脆性与细胞表面和细胞质标记物的相关性。我们建议与机械工程、细胞生物学和临床血液学专家合作，开发一种新的红细胞生物学技术，并展示其在遗传性球形红细胞增多症（HS）患者临床诊断中的适用性。为了实现这一目标，我们制定了以下具体目标：1)优化SiCMA室中的变形测量，2)将SiCMA变形分析与现有技术进行比较，以及3)在与红细胞病理相关的样品上测试新技术。成功的完成将导致建立一种新的方法，快速和高成本效益，选择，定义和关联异质再生细胞群体中单个细胞的细胞标记，用于膜生物学基础研究的实验室评估以及红细胞疾病的预后和治疗。

DESCRIPTION (provided by applicant): The unique ability of the red blood cell to deform and withstand the high shear stress in the circulation is lost with altered molecular interactions in te membrane or changes in the cytosol. We have developed a novel technique "Single Cell Micro-chamber Array" or SiCMA, to rapidly analyze heterogeneous cell populations, and plan to show that this technology will allow the correlation of deformation and fragility with cell surface and cytosolic markers in heterogeneous populations of red blood cells. We propose a multidisciplinary approach with experts from mechanical engineering, cell biology, and clinical hematology to develop a novel technology for red cell membrane biology and show its applicability for clinical diagnosis of patients with hereditary spherocytosis (HS). To reach this goal we have formulated the following specific aims: 1) To optimize deformation measurements in SiCMA chambers, 2) To compare SiCMA deformation analysis with established technology, and 3.) To test the new technology on samples relevant for red cell pathology. Successful accomplishment will lead to the establishment of a novel approach to rapidly and highly cost-effective, select, define, and correlate cellular markers of individual cells in a heterogeneous re cell population, to be used in laboratory assessment of basic research in membrane biology as well as for prognosis and treatment of red cell disorders.