CELLULAR MECHANICS AND MICROVASCULAR INTERACTION

在这个项目中，我们关注的是力学之间的相互关系， 黏附、信号和微血管流动。两个目标(目标1和2) 代表本供资期间的持续利息。目标1是 与红系机械功能异常的后果有关 细胞在微血管中的存活和流动。我们最近的调查结果是 日期证实了红色最重要的决定因素 细胞的生存能力在于它有足够的膜面积来包裹它的 在微血管系统的约束下的体积。在下一个时期 我们将继续利用专业知识的独特组合 并扩展这些研究，以确定 红细胞变形性异常对细胞分布和 微血管血流。第二个持续目标(目标2)与 发育正常的红系和微血管血流。第二 持续的目标(目标2)与正常红系的发育有关。 成熟后期的机械作用。相当大的初步 在这一目标方面取得了进展，因为有了一个新的 与高级骨髓专家David Wu博士合作 培养技术。通过将填充床细胞培养技术与 对未成熟的红系细胞进行微观机械测试，我们可以使 对了解红细胞前体细胞如何发育成熟的贡献 正常运作的细胞以及什么条件对正常的 发展膜的稳定性，这是红血球功能的关键。 具体目标3是基于以角色为中心的新兴趣 力学在强粘接触点的启动和稳定性中的作用 中性粒细胞和血管内皮细胞之间。尽管取得了重大进展 这是在白细胞和内皮细胞相互作用的研究中所做的， 关于涉及到的确切机制，仍然存在重大问题 确定相互作用和调节的特异性 从滚滚到止步到跳跃的过渡。微机械 对单个细胞的操作提供了无与伦比的能力来控制两者 细胞-细胞中的化学环境和机械力 相互作用，所以细胞力学在其中扮演的特定角色 粘接触点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的方法。

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.