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BIOMEMBRANE MECHANICS, SURFACE AFFINITY, AND ADHESION

生物膜力学、表面亲和力和粘附力

基本信息

批准号：
3338822
负责人：
EVAN A EVANS
金额：
$ 8.76万
依托单位：
UNIVERSITY OF BRITISH COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
1981
资助国家：
美国
起止时间：
1981-05-01 至 1987-04-30
项目状态：
已结题

项目摘要

The mechanical deformability properties of blood cells are not only essential determinants of flow distribution in the microcirculation but also modulate cell aggregation, agglutination, and other types of adhesive interactions. The initial stage of cell-surface "recognition" is quantitated by the chemical affinity between opposite surfaces; this is an important factor in removal of aberrant cells and material from the circulation, bacterial and viral infection of cells, and arrest and margination of circulating white cells and tumor cells. Viability of cell-cell contacts when exposed to disruption by shear forces in the circulation is related to the strength of adhesion which, in turn, depends on the extent of contact and the mechanics of separation. Hence, the objectives of this application are to quantitate the time-dependent mechanical properties of blood cells, the energetics of blood cell deformation and chemical attraction in cell-cell adhesion, and the mechanics of separation of adhesive contacts. The specific aims are to: (1) Relate the mechanical properties of blood granulocytes to the structural components of the cell; compare active and passive deformation properties of granulocytes; investigate membrane continuity and the degranulation process during cell activity; measure the motive force in phagocytosis and the effect of disruptors of cell structural components. (2) Measure the mechanical stiffening of red cell membranes caused by binding of adhesive ligands (e.g. "adhesins" shed from bacteria; agglutinating antibodies); measure the potential for formation of adhesive contact in these ligands; measure and model the detailed mechanics of separation of adhesive contacts; measure adhesivity of blood cells to cultured vascular endothelium. (3) Measure the kinetics and binding of fluorescently labelled ligands to single red cells; determine the relation between strength of adhesion, time course and magnitude of ligand binding; evaluate augmentation of adhesive strength by accumulation of material into cell-cell contact zones as cells are separated. Blood cell deformability and adhesion experiments utilize unique multi-micromanipulation techniques; the observations are recorded with a video-microscope system. Surface binding and kinetics of ligand-receptor complexes are measured with a laser microfluorometry system.

血细胞的机械变形性能不仅微循环中流量分布的基本决定因素，还调节细胞聚集、凝集和其他类型的粘附交互. 细胞表面“识别”的初始阶段是通过相对表面之间的化学亲和力来定量;这是一种在去除异常细胞和物质的重要因素，循环，细菌和病毒感染的细胞，并逮捕和循环白色细胞和肿瘤细胞的边缘。可行性当暴露于剪切力的破坏时，循环与粘附力有关，而粘附力又取决于接触的程度和分离的机制。所以本申请的目的是定量时间依赖性血细胞的力学性质，血细胞的能量学变形和化学吸引力的细胞-细胞粘附，粘合剂触点分离的力学。具体目的是：（1）研究血液的力学性质粒细胞的细胞的结构成分;比较活性和粒细胞的被动变形特性;研究膜连续性和细胞活动期间的脱粒过程;测量吞噬动力与细胞分裂剂的作用结构部件。 (2)测量红细胞的机械硬化由粘附配体结合引起的膜（例如，“粘附素”从细菌;凝集抗体）;测量形成这些配体中的粘附接触;测量和建模详细的力学粘附接触的分离;测量血细胞对培养的血管内皮细胞 (3)测量动力学和结合单个红细胞的荧光标记配体;测定粘附强度、时间进程和配体结合强度之间的关系; 评价通过材料累积到当细胞被分离时，细胞-细胞接触区。血细胞变形性和粘附实验利用独特的多显微操作技术;观察结果记录与视频显微镜系统配体-受体的表面结合和动力学用激光显微荧光测定系统测量复合物。