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

点击翻译按钮获取中文摘要

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.