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

Case Western Reserve University, Cleveland OH

Investigators

Abstract

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.