CELLULAR MECHANICS AND MICROVASCULAR INTERACTION

在这个项目中，我们专注于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） 代表本融资期的持续权益。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， 日期证实了这样的预期，即红色最重要的决定因素 细胞存活力是它有足够的膜面积来封闭它的 在微脉管系统的约束内的体积。今后一个时期 我们将继续利用独特的专业知识， 并扩展这些研究，以确定 异常的红细胞变形性影响细胞分布， 微血管血流第二个持续的目标（目标2）涉及到 正常红细胞和微血管流动的发展。第二 持续目标（目标2）与适当红系细胞的发育有关 机械功能在后期成熟。实质性初步 在这一目标方面取得了进展， 与高级骨髓专家大卫吴博士合作 养殖技术通过将填充床细胞培养技术与 微机械测试未成熟的红细胞，我们可以使重要的 有助于了解红细胞前体如何发育成成熟的 功能正常的细胞和什么条件是重要的， 膜稳定性的发展是红细胞功能所必需的。 具体目标3是基于一个新的兴趣集中的作用， 力学在强粘结接触的引发和稳定中的作用 中性粒细胞和内皮细胞之间的联系。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发现的， 关于所涉及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， 从滚动到停止再到渗出的过渡。微机械 操纵单细胞提供了无与伦比的能力， 细胞间的化学环境和机械力 相互作用，因此细胞力学在 粘附接触的形成和信号级联的产生 来改变和调节细胞的行为。

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.