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，可能会引起许多潜在的威胁生命的健康问题，包括镰状细胞性贫血，疟疾和糖尿病。当前，我们对红细胞特性如何影响其粘性的理解受到限制。该研究项目结合了理论，数学模型和实验，以尝试对导致细胞粘合到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加现有的外展计划，该计划与当地灾难社区的高中学生参与研究机会，实验室旅行和嘉宾讲座。针对普通人群的YouTube视频和研讨会正在进一步将对这项工作的理解扩大给更广泛的受众，与该项目相关的实验模块的开发和交付也是如此。这项灵活的教育和培训计划旨在帮助发展生物医学和医疗保健领域不断扩展的需求所需的劳动力。这项研究的中心假设是红细胞的变形性是细胞附着和脱离过程的关键因素，其中低稳态细胞与粘附分子具有更稳定的接触，从而增强了红细胞与内皮细胞的粘附强度。为了验证该假设，该项目的具体研究目的是：（i）通过新型的Lagrangian流体互动模型和微粒子图像速度实验中的单个单层互动模型和微生物效应的效率驱动的效率和定量的效率，并定量了微纤维型的效率，从而得出了对红细胞内皮相互作用相互作用的液体机制的基本理解。在不同流动条件下的血浆； （ii）使用集成的微流体实验和细胞尺度的流体结构相互作用模拟来表征身体条件下健康和不健康细胞的机械性能和可变形性； （iii）通过在血浆和微氟实验中的三维直接细胞模拟结合结合了定性和定量描述细胞变形性对固定的内皮蛋白质的潜在物理学的影响。研究人员正在专注于更好地理解细胞的形状，变形性和膜特性的灵敏度，受体配体键的类型和密度以及血浆的物理剪切速率，对红细胞 - 内皮粘合剂的动态强度。该项目将推进计算科学，生物力学的知识库，并开发新的实验技术来治疗血管疾病。