Final Paper pdf 1.7MB

Capstone Project – Design of A Novel Flow Chamber To Study The Effects of Vascular Stiffness On Migration of Blood-Borne Cells

Cell rolling on vascular endothelium is critical for many physiological and pathological processes. Atherosclerosis is a pathological disorder characterized by stiffening of vascular walls due the growth of lipid-rich lesions. Leukocytes are the mobile keepers of the immune system and are found in abundance within atherosclerosis-prone aortas. Despite numerous studies, understanding the mechanism of leukocyte homing in growing lesions remains a challenge. Leukocyte adhesion begins with rolling along endothelium due to the specific binding between selectin receptors on endothelial cells and their complementary ligands expressed on the surface of leukocytes. Binding to selectin regulates the capture of leukocytes in the face of dislodging hemodynamic forces during their random encounters with endothelium. Progression of atherosclerotic plaques is followed by stiffening of the aortic wall. The effect of substrate stiffness on leukocytes rolling is not particularly well documented in the literature. The primary objective of this capstone project was to design a novel flow chamber to examine the effect of substrate stiffness on the kinematics of leukocyte motion. The team was formed by students with different majors (Mechanical and Biomedical Engineering) to work on a cross-disciplinary research project. The central hypothesis was that leukocytes roll with a higher velocity over softer substrates. This hypothesis was tested in vitro using a flow chamber with soft and rigid substrates. The rigid portion of the substrate was made by 3D printing of a transparent resin and its flexible portion was made of polyacrylamide gel. The design was tested by measuring the migration velocity of flowing leukocytes using video-microscopy. Students benefited from the cross-disciplinary nature of this research. Specifically, they learned about the physics of biological adhesion, the mechanics of leukocyte migration, and how to implement the basic principles of fluid mechanics to design a device with biomedical applications.