CELLULAR MECHANICS AND MICROVASCULAR INTERACTION

细胞力学和微血管相互作用

• 批准号: 6327696
• 负责人: Richard E Waugh
• 金额: $ 25.82万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-11 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6327696
• 关键词: blood viscosity; bone marrow; cell adhesion; cell differentiation; cell morphology; cell senescence; clinical research; erythrocyte membrane; erythrocytes; erythropoiesis; hemodynamics; human subject; laboratory mouse; membrane activity; membrane structure; microcirculation; tissue /cell culture

In this project we focus on the inter-relationships among mechanics, adhesion, signaling, and microvascular flow. Two aims (Aims 1 and 2) represent continuing interests from the present funding period. Aim 1 is related to the consequences of abnormal erythroid mechanical function on cell survival and flow in the microvasculature. Our recent findings to date confirm the expectation that the most important determinant of red cell viability is that it have sufficient membrane area to enclose its volume within the constrains of the microvasculature. In the next period we will continue to take advantage of the unique combination of expertise in this program and extend these studies to determine the impact that abnormal erythrocyte deformability has on cell distribution and microvascular flow. The second continuing aim (Aim 2) is related to development of proper erythroid and microvascular flow. The second continuing aim (Aim 2) is related to the development of proper erythroid mechanical function during late-stage maturation. Substantial preliminary progress has been made with regard to this aim because of a new collaboration with Dr. David Wu, who is expert on advanced bone marrow culture technology. By combining packed bed cell culture techniques with micromechanical testing of immature erythroid cells, we can make important contributions to understanding how red cell precursors develop into mature functioning cells and what conditions are important for the proper development of membrane stability that is essential for red cell function. Specific Aim 3 is based on a new interest centered on the role that mechanics play in the initiation and stability of strong adhesive contacts between neutrophils and endothelium. In spite of the significant progress that has been made in studies of leukocyte-endothelial cell interactions, significant questions remain about the precise mechanisms involved in determining the specificity of interaction and regulation of the transition from rolling to arrest to diapedesis. Micromechanical manipulation of single cells provides unparalleled ability to control both the chemical environment and the mechanical forces involved in cell-cell interactions, so that the specific role that cellular mechanics plays in the formation of adhesive contacts and the generation of signaling cascade to modify and regulate cell behavior can be deduced.

在这个项目中，我们关注力学之间的相互关系， 粘附，信号传导和微血管流动。两个目标（目标1和2） 代表当前资金期间的持续利益。目标1是 与异常的红细胞机械功能对后果有关 细胞存活和微脉管系统中的流量。我们最近的发现 日期证实了红色最重要决定因素的期望 细胞活力是它具有足够的膜区域来包围 微脉管系统约束内的体积。在下一个时期 我们将继续利用专业知识的独特组合 在该计划中并扩展了这些研究，以确定 异常红细胞可变形性在细胞分布和 微血管流动。第二个持续目标（AIM 2）与 发展适当的红细胞和微血管流动。第二个 持续的目标（AIM 2）与适当的红斑的发展有关 晚期成熟期间的机械功能。实质性初步 由于一个新的目标，在这个目标方面取得了进展 与高级骨髓专家David Wu博士合作 文化技术。通过将包装的床细胞培养技术与 未成熟的红细胞细胞的微力学测试，我们可以使重要 对了解红细胞前体如何发展成成熟的贡献 功能性细胞以及哪些条件对于适当的 膜稳定性的发展，这对于红细胞功能至关重要。 具体目标3是基于以此为中心的新兴趣 力学在强胶接触的启动和稳定性方面发挥了作用 在中性粒细胞和内皮之间。尽管取得了重大进展 这是在白细胞 - 内皮细胞相互作用的研究中做出的， 关于涉及的确切机制仍然存在重大问题 确定相互作用的特异性和调节 从滚动到逮捕到二静脉的过渡。微电机械 单个单元的操纵提供了无与伦比的控制能力 化学环境和涉及细胞细胞的机械力 相互作用，使细胞力学在 粘合触点的形成和信号级联的产生 可以推导修改和调节细胞行为。