CELLULAR MECHANICS AND MICROVASCULAR INTERACTION

细胞力学和微血管相互作用

• 批准号: 6470095
• 负责人: Richard E Waugh
• 金额: $ 11万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6470095
• 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，我们重点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） 代表当前资助期间的持续利益。目标 1 是 与红细胞机械功能异常的后果有关 微血管中的细胞存活和流动。我们最近的发现 日期证实了红色最重要的决定因素的期望 细胞活力是指它有足够的膜面积来包围其细胞 体积在微脉管系统的限制内。在接下来的一段时间内 我们将继续利用独特的专业知识组合 在此计划中并扩展这些研究以确定其影响 异常的红细胞变形能力对细胞分布和 微血管血流。第二个持续目标（目标 2）与 适当的红细胞和微血管血流的发育。第二个 持续目标（目标 2）与适当红细胞的发育有关 后期成熟期间的机械功能。实质性初步 由于新的目标，这一目标已取得进展 与高级骨髓专家David Wu博士合作 文化技术。通过将填充床细胞培养技术与 未成熟红细胞的微机械测试，我们可以做出重要的 对理解红细胞前体如何发育成熟的贡献 功能细胞以及哪些条件对正常细胞很重要 膜稳定性的发展对于红细胞功能至关重要。 具体目标 3 基于以以下角色为中心的新兴趣： 力学在强力粘合接触的引发和稳定性中发挥着作用 中性粒细胞和内皮细胞之间。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取得的， 关于其中所涉及的精确机制仍然存在重大问题 确定相互作用和调节的特异性 从滚动到停止再到血渗的过渡。微机械 单细胞的操纵提供了无与伦比的控制能力 细胞间涉及的化学环境和机械力 相互作用，因此细胞力学在其中发挥的特定作用 粘合接触的形成和信号级联的产生 可以推断出改变和调节细胞行为。