MECHANICAL ASPECTS OF BLOOD CELL MATURATION AND CIRCULATION

本项目的总体目标是在定量层面上了解 细胞变形能力和机械功能在循环中的作用 在正常和病理条件下。PI的广泛利益 包括红细胞、嗜中性粒细胞和永生细胞的功能。 被认为是模仿这些细胞行为的细胞系。这个项目 着重于红系细胞的特性和功能 脉 中性粒细胞粘附的机械方面的研究是 项目1提出。涉及红细胞的研究领域 (this项目）范围从细胞成熟和骨髓排出， 衰老和细胞从循环中消失。变化 细胞尺寸是红细胞成熟和老化过程中的特性， 将与M. Snyder（马萨诸塞州波士顿的马萨诸塞大学医学中心）使用狒狒作为模型 系统此外，明确定义的细胞力学的影响， 微循环中细胞存活和流动的异常将是 在小鼠中进行测量，以确定异常 变形性和异常变形性的后果 微循环血流在进行这些调查时，科瑙夫博士 将开发改变和稳定细胞体积的策略。 沃将测量这些和其他修改细胞的结果， 尺寸和机械性能。 与Project 5合作 (Dr. Cokelet）的变形能力改变对细胞分布的影响， 将建立体外模型网络，并与 项目4（Sarelius博士）这些改变对生存的影响 这些细胞在活体脉管系统中的分布 决定。体液因素的重要性和 出血应激对红细胞膜发育的影响 在成熟后期的机械功能将被评估， 特别关注双层-骨架界面的稳定性， 膜剪切弹性的适当发展。 最后 假设在成熟过程中细胞变形能力的变化是 调节细胞从骨髓排出的重要因素 将被评估。我们将利用国家资源 康奈尔大学的纳米纤维设施，以获得薄圆形 硅晶片上的孔来模拟骨髓的几何形状 细胞必须通过的内皮孔，并决定细胞的功能。 骨髓红系细胞传代对孔径和压力的依赖性 不同成熟度的细胞。

The general aim of this project is to understand at a quantitative level the role of cell deformability and mechanical function in the circulation under normal and pathological conditions. The broad interests of the PI's encompass the function of red blood cells, neutrophils and immortalized cell lines thought to mimic the behavior of these cells. This project focusses on the properties and function of cells from the erythroid lineage. Studies of the mechanical aspects of neutrophil adhesion are proposed with Project 1. The areas of investigation involving red cells (this project) range from cell maturation and bone marrow egress to senescence and disappearance of cells from the circulation. Changes in cell dimensions are properties during red cell maturation and aging under normal conditions in vivo will be measured in collaboration with Dr. M. Snyder (UMASS Medical Center, Boston, MA) using the baboon as a model system. In addition, the effects of well-defined cellular mechanical abnormalities on cell survival and flow in the microcirculation will be measured in the mouse to establish the tolerable limits for abnormal deformability and the consequences of abnormal deformability on microcirculatory blood flow. In pursuing these investigations, Dr. Knauf will develop strategies for altering and stabilizing cell volume, and Dr. Waugh will measure the results of these and other modifications on cell dimensions and mechanical properties. In collaboration with Project 5 (Dr. Cokelet) the effects of altered deformability on cell distribution in model networks in vitro will be established, and in cooperation with Project 4 (Dr. Sarelius) the effects of these alterations on the survival and distribution of these cells in the living vasculature will be determine. The importance of humoral factors and the effects of hemorrhagic stress on the development of proper red cell membrane mechanical function during late stage maturation will be assessed with particular focus on the stability of the bilayer-skeletal interface and the proper development of membrane shear elasticity. Finally, the hypothesis that changes in cell deformability during maturation are a significant factor in the regulation of cell egress from the bone marrow will be evaluated. We will take advantage of the resources at the National Nanofabrication Facility at Cornell University to obtain thin circular apertures in silicon wafers to model the geometry of the marrow endothelial pores through which the cells must pass and determine the dependence of cell passage on pore size and pressure for marrow erythroid cells of different maturities.