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

Freund 0932607白细胞（白色细胞）粘附到微循环中的内皮上是炎症反应的关键组成部分，如果过度活跃，则可能成为危及生命的医学病症。流体力学相互作用是这个过程的核心。已经取得了相当大的进展，在建模的结合动力学的滚动和坚定的粘附阶段，白细胞上的微绒毛的作用，和白细胞的粘弹性的重要性。然而，由于血液的颗粒特性，白细胞所经历的不稳定的流体动力尚不清楚，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。 那些考虑多个细胞的人已经在理想化的几何形状中这样做了，并且忽略了红细胞的高体积密度和高柔性，这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。理解细胞间流体动力学相互作用对白细胞转运的影响将是这项工作的主要智力价值。不稳定的细胞-细胞相互作用力预计将出现作为一个随机强迫，将耦合随机结合动力学。PI将使用PI最近开发的最先进的O（N log N）边界积分求解器来研究这些问题的影响。它将红细胞模拟为逼真的柔性壳膜，并已根据血流的可用数据进行了定量验证。PI表明，它可以再现微循环中白细胞转运的一些关键方面，并且将在本研究中进行调整以包括粘附。该算法已被证明是有效的，足以提供所需的滚动和结合动力学的数百个红细胞的统计数据。流动血液中的微米级力比本研究关注的白细胞运输和粘附更重要。癌症转移可能涉及细胞或细胞簇的提升、运输和再附着，这些预期由均质化模型无法描述的细胞-细胞相互作用力介导。凝血过程中的血小板活化是另一个类似的重要现象。这项研究也将影响微流体系统处理细胞或工程颗粒的设计。PI在这一领域的影响将通过以“干净”的方式向社区提供代码来扩大，以便用户可以添加和分析结合动力学。该软件包将作为PI教授的细胞生物力学研究生课程的一部分进行开发和测试。

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.