HYDRODYNAMIC INTERACTIONS BETWEEN ADHERING NEUTROPHILS

粘附的中性粒细胞之间的流体动力学相互作用

• 批准号: 6388773
• 负责人: Michael R. King
• 金额: $ 2.99万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6388773
• 关键词: cell adhesion; cell cell interaction; fluidity; integrins; mathematical model; model design /development; neutrophil

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.

该项目将检查细胞 - 细胞相互作用在何种程度上影响炎症部位中嗜中性粒细胞的积累。配体涂层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本质上是嘈杂的，并且间歇性停顿在运动中。这些暂停使整联蛋白键形成，坚持滚动的细胞以进行后续的渗出。我们假设细胞碰撞和集中悬浮流变性会影响滚动的动力，从而影响了向坚定逮捕的过渡。为了检验该假设，一种新型的计算技术将用于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的化学相互作用的定量模型。与先前研究的细胞或涂层珠的浓度相比，将通过流动室实验进行测试，将通过流量室实验进行测试。这项研究旨在弥合白细胞滚动的体外和体内观察之间的差距，特别是，在体内较高的剪切应力下，滚动行为得到了支持。