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

当红细胞粘在血管壁上时，可能会产生一些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。目前，我们对红细胞特性如何影响其粘性的了解有限。这项研究项目结合了理论、数学模型和实验，试图对导致细胞黏附到血管壁的机制进行准确的描述。参与该项目的研究人员正在参与一个现有的推广计划，该计划让来自当地弱势社区的高中生参与研究机会、实验室参观和客座讲座。针对普通民众的YouTube视频和讲习班进一步扩大了对这项工作的了解，与这一项目有关的实验单元的开发和交付也是如此。这一灵活的教育和培训计划旨在帮助培养所需的劳动力，以满足生物医学和医疗保健领域不断增长的需求。本研究的中心假设是，红细胞变形性是细胞附着和分离过程中的一个关键因素，其中低变形性细胞与黏附分子有更稳定的接触，从而增强红细胞与内皮的黏附强度。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体-结构相互作用模型和微流体通道中的微粒子图像测速实验，对红细胞内皮细胞相互作用附近的流体力学有一个基本的了解，并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健康和不健康细胞在生理条件下的力学性质和变形能力；以及(Iii)通过结合等离子体中的三维直接细胞模拟和微流控实验，定性和定量地描述细胞变形性对流动的红细胞与固定的内皮蛋白黏附的基本物理过程的影响。研究人员正致力于更好地了解细胞的形状、变形性和膜特性、受体-配体键的类型和密度以及血浆的生理剪切率对红细胞-内皮黏附动态强度的敏感性。该项目将推进计算科学、生物力学的知识基础，并开发治疗血管疾病的新实验技术。

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.