COMPUTATIONAL MODELING AND SIMULATION OF RECEPTOR-MEDIATED LEUKOCYTE ROLLING AD

受体介导的白细胞滚动广告的计算建模与模拟

• 批准号: 7956176
• 负责人: PROSENJIT BAGCHI
• 金额: $ 0.08万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956176
• 关键词: Address; Adhesions; Atherosclerosis; Biomedical Research; Blood capillaries; Blood flow; Cell Adhesion; Cell membrane; Cell-Cell Adhesion; Cells; Complex; Computational Technique; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Computing Methodologies; Coupled; Elements; Endothelium; Environment; Equilibrium; Funding; Grant; High Performance Computing; Inflammation; Inflammatory Response; Injury; Institution; Integrins; Labyrinth fenestration; Leukocyte Rolling; Leukocytes; Ligands; Liquid substance; Mediating; Membrane; Methods; Molecular; Monte Carlo Method; Motion; Nature; Plasma; Process; Property; Research; Research Personnel; Resources; Selectins; Simulate; Site; Source; Tissues; United States National Institutes of Health; Vascular Endothelium; base; capillary; driving force; fluid flow; leukocyte homing; models and simulation; nanoscale; receptor; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Leukocyte homing in past-capillary vessels is critical in inflammatory response of the body during tissue injury, attack by foreign elements, or even in case of atherosclerosis. Through a complex multi-step process, circulating leukocytes are captured from the flowing blood in to the vascular endothelium. Mediated by selectin molecules expressed on the leukocyte membrane and on endothelial, leukocytes perform slow rolling. Subsequently, leukocytes are firmly adhered by integrin molecules, and transmigrate through endothelial fenestration to the sites of inflammation or tissue injury. The selectin-mediated slow rolling of leukocytes is crtical as it allows the cells to `search( for targeted sites. Leukocyte rolling and adhesion occurs under a balance between the hydrodynamic force of the blood flow, and the adhesion force of the receptor/ligand bonds formed between the cell membrane and the endothelium. The proceess is of multiscale in nature -- the macroscopic motion of the blood plasma provides the driving force, whereas the nanoscale adhesion force provide the stability of the cells. In order to understand how under the hydrodynamic dispersive forces, the selectin bonds mediate cell rolling, we plan to develop a multi-scale computational technique to address cell/substrate and cell/cell adhesion under hydrodynamic flowing condition. The computational method will consist of three-dimensional fluid flow solver (navier-Stokes solver) based on immersed boundary method to consider deformation of the cell during its adhesion to endothelium. The macroscopic fluid dynamics will be coupled to the molecular bond formation by stochastic simulation in which formation of selectin bonds will be simulated by Monte Carlo method. The research will elucidate how cellular properties, and biophysical parameters of selectin bonds promote cell adhesion under a stressful hydrodynamic environment.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 白细胞在毛细血管后的归巢在组织损伤、异物攻击或甚至动脉粥样硬化的情况下的身体炎症反应中是至关重要的。通过复杂的多步骤过程，循环白细胞从流动的血液中被捕获到血管内皮中。通过白细胞膜和内皮细胞上表达的选择素分子介导，白细胞进行缓慢滚动。随后，白细胞被整联蛋白分子牢固地粘附，并通过内皮穿孔迁移到炎症或组织损伤部位。选择素介导的白细胞缓慢滚动是至关重要的，因为它允许细胞“搜索”（靶向位点）。白细胞滚动和粘附在血流的流体动力学力与细胞膜和内皮之间形成的受体/配体键的粘附力之间的平衡下发生。这个过程本质上是多尺度的--血浆的宏观运动提供驱动力，而纳米级的粘附力提供细胞的稳定性。为了理解在流体动力学分散力作用下，选择素键如何介导细胞滚动，我们计划发展一种多尺度计算技术来解决流体动力学流动条件下的细胞/基质和细胞/细胞粘附。计算方法将包括基于浸没边界法的三维流体流动求解器（Navier-Stokes求解器），以考虑细胞粘附至内皮期间的变形。通过随机模拟将宏观流体动力学耦合到分子键的形成，其中选择素键的形成将通过Monte Carlo方法模拟。这项研究将阐明细胞特性和选择素键的生物物理参数如何在压力流体动力学环境下促进细胞粘附。