The multi-cell fluid mechanics of white cell transport in microvessels

微血管中白细胞运输的多细胞流体力学

• 批准号: 0932607
• 负责人: Jonathan Freund
• 金额: $ 27.81万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0932607&HistoricalAwards=false
• 关键词: multi; cell; fluid; mechanics; white

Freund0932607Leukocyte (white cell) adhesion to the endothelium in the microcirculation is a key component of the inflammation response, which if overactive can become a life threatening medical condition. Fluid mechanic interactions are central to this process. Considerable progress has been made in modeling the binding kinetics of the rolling and firm-adhesion stages, the role of microvilli on the leukocyte, and the importance of the viscoelastic properties of the leukocyte. However, the unsteady hydrodynamic forces experienced by the leukocyte due to the particulate character of blood are not understood and are needed for a complete description of the process. Most models use simple homogenization of the flowing blood. Those considering multiple cells have done so in idealized geometries and have neglected the high volume densities and high flexibility of the red cells that give blood its unique properties. On the scale of the leukocyte, there is clear experimental evidence--both in vitro and in vivo--that interactions with red cells are important. Understanding the effect of cell-cell hydrodynamic interactions on leukocyte transport will be the principal intellectual merit of this work. The unsteady cell-cell interaction forces are expected to appear as a stochastic forcing that will couple with the stochastic binding kinetics. The PI will examine the implications of these using a state-of-the-art O(N log N) boundary integral solver developed recently by the PI. It models red cells as realistically flexible shell membranes and has been validated quantitatively against available data for blood flow. The PIs have shown that it can reproduced some key aspects of leukocyte transport in the microcirculation and it will be adapted to include adhesion in this study. The algorithm has been demonstrated to be efficient enough to provide the statistical data needed for rolling and binding kinetics for hundreds of red blood cells. The micron-scale forces in flowing blood are important beyond the leukocyte transport and adhesion on which this study focuses. Cancer metastasis can involve lift up, transport, and reattachment of cells or cell clusters that are expected to be mediated by cell-cell interaction forces that homogenized models cannot describe. Platelet activation in blood clotting is another similarly important phenomenon. This study will also impact the design of microfluidic systems processing either cells or engineered particles. The PI's impact in this area will be broadened by providing the code to the community in a "clean" way such that binding kinetics can be added by a user and analyzed. This package will be developed and tested as a component of a graduate course on cellular biomechanics taught by the PI.

白细胞与微循环内皮的粘附是炎症反应的关键组成部分，如果过度活跃可能会成为威胁生命的疾病。流体力学相互作用是这一过程的核心。在模拟滚动和牢固粘附阶段的结合动力学，微绒毛对白细胞的作用以及白细胞粘弹性特性的重要性方面取得了相当大的进展。然而，由于血液的颗粒特性，白细胞所经历的非定常流体动力尚未被理解，并且需要对该过程进行完整的描述。大多数模型使用流动血液的简单均质化。那些考虑多细胞的人是在理想化的几何形状中这样做的，而忽略了红细胞的高体积密度和高灵活性，正是它们赋予了血液独特的特性。在白细胞的规模上，有明确的实验证据——在体外和体内——与红细胞的相互作用是重要的。理解细胞-细胞流体动力学相互作用对白细胞运输的影响将是这项工作的主要智力价值。非定常细胞-细胞相互作用力预计表现为随机作用力，将与随机结合动力学耦合。PI将使用PI最近开发的最先进的O（N log N）边界积分求解器来检查这些问题的含义。它将红细胞建模为实际的柔性壳膜，并已根据可用的血流数据进行了定量验证。pi已经表明，它可以复制微循环中白细胞运输的一些关键方面，并且它将在本研究中适应包括粘附。该算法已被证明是有效的，足以提供所需的统计数据滚动和结合动力学数百红细胞。在流动的血液中的微米尺度的力量是重要的超越白细胞运输和粘附，这是本研究的重点。癌症转移可能涉及细胞或细胞簇的抬升、运输和再附着，这些被认为是由细胞-细胞相互作用力介导的，而均质模型无法描述。凝血过程中的血小板活化是另一个同样重要的现象。这项研究也将影响处理细胞或工程颗粒的微流体系统的设计。通过以一种“干净”的方式向社区提供代码，使得用户可以添加并分析结合动力学，PI在这一领域的影响将得到扩大。这个包将被开发和测试，作为由PI教授的细胞生物力学研究生课程的一个组成部分。