HYDRODYNAMIC INTERACTIONS BETWEEN ADHERING NEUTROPHILS

该项目将研究细胞间的相互作用在多大程度上影响炎症部位中性粒细胞的聚集。流室实验表明，选择素介导的白细胞滚动本身就有噪音，运动时会有间歇性停顿。这些停顿使整合素键形成，牢牢地附着在一个滚动的细胞上，以便随后的外渗。我们假设，细胞碰撞和集中悬浮流变学会影响滚动的动力学，从而影响到稳固止步的转变。为了验证这一假设，将使用一种新的计算技术来直接模拟多细胞系统中的细胞黏附。流体中细胞相互作用的流体动力学将使用斯托克斯动力学方法，结合细胞与底物之间的化学相互作用的定量模型进行严格计算。得到的理论预测将通过使用比以前研究的更高浓度的电池或涂层珠子的流室实验来验证。这项研究旨在弥合体外和体内观察到的白细胞滚动之间的差距，具体地说，在体内更高的剪应力下支持滚动行为。

This project will examine to what extent cell-cell interactions affect the accumulation of neutrophilis at a site of inflammation. Flow chamber experiments with both ligand-coated hard spheres and neutrophilis show that selectin-mediated leukocyte rolling is inherently noisy, with intermittent pauses in motion. These pauses allow integrin bonds to form, firmly adhering a rolling cell for subsequent extravasation. We hypothesize that cell collisions and concentrated suspension rheology influence the dynamics of rolling, and thus, the transition to firm arrest. To test this hypothesis a novel calculational technique will be used to directly simulate cell adhesion in a multi-cell system. The hydrodynamics of cellular interactions in the fluid will be rigorously calculated using the Stokesian Dynamics method, combined with a quantitative model of the chemical interactions between cell and substrate. The resulting theoretical predictions will be tested with flow chamber experiments using a higher concentration of cells or coated beads than has been previously studied. This study is intended to bridge the gap between in vitro and vivo observations of leukocyte rolling, specifically, that rolling behavior is supported at much higher shear stresses in vivo.