Deformability distributions in heterogeneous red blood cell populations

异质红细胞群的变形能力分布

• 批准号: 8606500
• 负责人: Frans A. Kuypers
• 金额: $ 20.03万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-18 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8606500
• 关键词: Basic Science; Binding; Biochemical; Biology; Blood Circulation; Blood specimen; Cell Count; Cell Shape; Cell membrane; Cell surface; Cells; Cellular biology; Clinical; Clinical Data; Computer software; Cytolysis; Cytosol; Data; Diagnosis; Diagnostic; Disease; Electromagnetics; Engineering; Enzymes; Erythrocytes; Fluorescence; Gene Mutation; Genetic; Goals; Hematology; Hereditary Spherocytosis; Hospitals; Human; Image Analysis; Individual; Label; Laboratories; Lead; Measurement; Measures; Mechanics; Membrane; Membrane Biology; Methods; Microscopy; Morphology; Mus; Optics; Osmotic Fragility test; Pathology; Patients; Population; Population Heterogeneity; Reaction; Relative (related person); Reporting; Research; Sampling; Sickle Cell Anemia; Signal Transduction; Stress; Techniques; Technology; Testing; Thalassemia; biological research; clinical Diagnosis; clinical application; clinically relevant; cost effective; design; improved; interdisciplinary approach; new technology; novel; novel strategies; outcome forecast; public health relevance; shear stress

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.

描述（由申请人提供）：红细胞变形和承受循环中高剪切应力的独特能力随着TE膜中的分子相互作用的改变或细胞质变化而丢失。我们开发了一种新型技术“单细胞微芯阵列”或SICMA，以迅速分析异质细胞种群，并计划表明该技术将允许在红细胞异质群体中变形和脆弱性与细胞表面和胞质标记的相关性。我们提出了一种多学科方法，该方法对机械工程，细胞生物学和临床血液学的专家进行了多学科方法，以开发一种用于红细胞膜生物学的新技术，并显示了其适用于遗传性球形细胞增多症患者（HS）的临床诊断。为了实现这一目标，我们制定了以下特定目的：1）优化SICMA腔室中的变形测量​​，2）将SICMA变形分析与既定技术进行比较，以及3.）测试与红细胞病理相关的样品的新技术。成功的成就将导致建立一种新型的方法，以快速，成本效益，选择，定义和相关，将单个细胞的细胞标记物在异质的RE细胞种群中，可用于膜生物学基础研究以及预后和治疗红细胞障碍的实验室评估。