An integrated experimental and computational study of erythrocyte adhesion mechanics in blood flows

血流中红细胞粘附力学的综合实验和计算研究

• 批准号: 1706295
• 负责人: Bo Li
• 金额: $ 39.99万
• 依托单位: Case Western Reserve University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1706295&HistoricalAwards=false
• 关键词: integrated; experimental; computational; study; erythrocyte

When red blood cells stick to the walls of blood vessels, a number of potentially life-threatening health problems can be created, including sickle-cell anemia, malaria, and diabetes. Currently, our understanding of how red blood cell properties influence their stickiness is limited. This research project combines theory, mathematical models and experiments to try to develop an accurate description of the mechanisms that lead to cell adhesion to blood vessel walls. The researchers involved in this project are participating in an existing outreach program that engages high school students from local disadvantaged communities in research opportunities, lab tours, and guest lectures. YouTube videos and workshops targeted at the general population are further extending the understanding of this work to a broader audience, as are the development and delivery of experimental modules related to this project. This flexible educational and training program is intended to help develop the workforce needed to address expanding demands in the field of biomedical science and healthcare. The central hypothesis of this study is that erythrocyte deformability is a key factor in cell attachment and detachment processes, wherein low-deformability cells have more stable contact with the adhesion molecules, which enhances the adhesion strength of erythrocyte to endothelium. To verify the hypothesis, the specific research aims of this project are: (i) to derive a fundamental understanding of the fluid mechanics in the vicinity of erythrocyte endothelium interactions by a novel monolithic Lagrangian Fluid-Structure Interaction model and micro-Particle Image Velocimetry experiments in microfluidic channels, and quantify the lift and drag forces on the deformable cells exerted by the plasma under different flow conditions; (ii) to use integrated microfluidic experiments and cell-scale Fluid-Structure Interaction simulations to characterize the mechanical properties and deformability of healthy and unhealthy cells in physiological conditions; and (iii) to qualitatively and quantitatively describe the influence of cell deformability on the underlying physics of flowing erythrocyte adhesion to immobilized endothelium proteins by a combination of three-dimensional direct cell simulations in plasma and microfluidic experiments. The researchers are focusing on better understanding the sensitivities of the shape, deformability and membrane properties of cells, the type and density of receptor-ligand bonds, as well as the physiological shear rates of plasma, on the dynamic strength of erythrocyte-endothelium adhesion. This project will advance the knowledge base in computational science, biomechanics and develop new experimental technologies to treat vascular disease.

当红细胞粘在血管壁上时，可能会产生许多潜在的危及生命的健康问题，包括镰状细胞性贫血、疟疾和糖尿病。目前，我们对红细胞特性如何影响其粘性的理解是有限的。该研究项目将理论、数学模型和实验相结合，试图对导致细胞粘附血管壁的机制进行准确描述。参与该项目的研究人员正在参与一项现有的外展计划，该计划邀请来自当地弱势社区的高中生参加研究机会、实验室参观和客座讲座。针对普通大众的YouTube视频和讲习班正在进一步将这项工作的理解扩展到更广泛的受众，与此项目相关的实验模块的开发和交付也是如此。这种灵活的教育和培训计划旨在帮助发展应对生物医学科学和医疗保健领域不断扩大的需求所需的劳动力。本研究的中心假设是红细胞变形能力是细胞附着和脱离过程的关键因素，低变形能力的细胞与粘附分子的接触更稳定，从而增强了红细胞对内皮的粘附强度。为了验证这一假设，本项目的具体研究目标是：(i)通过新颖的整体拉格朗日流固相互作用模型和微流控通道中的微粒子图像测速实验，对红细胞内皮相互作用附近的流体力学有基本的认识，量化不同流动条件下等离子体对可变形细胞的升力和阻力；（ii）利用集成微流体实验和细胞尺度的流体-结构相互作用模拟来表征生理条件下健康和不健康细胞的力学特性和可变形性；（iii）通过结合等离子体和微流体实验中的三维直接细胞模拟，定性和定量地描述细胞可变形性对流动红细胞粘附于固定内皮蛋白的潜在物理特性的影响。研究人员的重点是更好地了解细胞的形状、可变形性和膜特性的敏感性，受体-配体键的类型和密度，以及血浆的生理剪切速率，以及红细胞-内皮细胞粘附的动态强度。该项目将推进计算科学、生物力学的知识基础，并开发新的实验技术来治疗血管疾病。