HYDRODYNAMIC INTERACTIONS BETWEEN ADHERING NEUTROPHILS

这个项目将检查细胞间相互作用在多大程度上影响炎症部位中性粒细胞的积累。配体包覆的硬球和中性粒细胞的流动室实验表明，选择素介导的白细胞滚动具有固有的噪声，在运动中具有间歇性停顿。这些停顿使整合素键形成，牢固地附着在滚动细胞上，以便随后外溢。我们假设细胞碰撞和集中的悬浮液流变影响滚动的动力学，因此，过渡到坚定的逮捕。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粘附。流体中细胞相互作用的流体动力学将使用Stokesian动力学方法严格计算，并结合细胞与底物之间化学相互作用的定量模型。由此产生的理论预测将通过流动室实验进行测试，使用比以前研究的更高浓度的细胞或涂覆珠。本研究旨在弥合体外和体内白细胞滚动观察之间的差距，特别是在体内更高的剪切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.