Harry Goldsmith Presentation Title: Observing Human Blood Cells in Flow through Microchannels Abstract: For the rheologist, blood is essentially a concentrated suspension of biconcave 8-µm diameter red cells (40% by volume) that circulates within the body in vessels from 25 mm down to 5 µm diameter. Here, we describe in vitro tracking of blood cells in a travelling microtube apparatus and in a counter-rotating micro cone-plate device at low Reynolds numbers. Observations of the flow behavior of individual red cells reveal a marked and continuously changing deformation and interaction of the cells in shear, and this, together with their migration away from the vessel wall accounts for the low whole blood overall viscosity compared to other concentrated suspensions and emulsions. Red cells also strongly affect the flow behavior and interactions of platelets and of white cells, which although present at much lower concentrations (0.3% by volume), play key roles in thrombosis, hemostasis, and inflammation. Studies of the kinetics of the formation and break-up of receptor-ligand bonds between membranes of platelets and of white cells in shear flow revealed single bond strengths of 50 -200 nN. Such micro image particle velocimetry (µPIV) studies have recently been considerably refined and extended to in vivo vessels such as postcapillary venules. Using submicron fluorescent latex spheres, the existence of an impermeable and hydrodynamically effective surface layer (< 0.5 µm thick) extending out from the vessel endothelium has been confirmed. The lecture is illustrated by movies of blood flow in vitro and in vivo. Biography: Dr. Goldsmith's research was first concerned with the microrheology of human blood, in particular that of the red cell (RBC) using a travelling microtube to track and photograph the cells in flow through microtubes using high resolution microscopy. RBC are subjected to shear stress and considerable particle crowding, and are continually distorted from the biconcave resting shape. The striking deformation of RBC at normal hematocrits is the microscopic correlate of the macroscopic low viscosity of blood. Continuous interactions between RBC produce a mixing flow and an increased rate of cell-wall collisions, important for normal vessel wall repair as well as in the genesis of atherosclerosis and thrombosis. This led to a study of the growth of platelet aggregates as a function of the applied shear stress, and to distinguish the separate roles of fibrinogen and von Willebrand factor, the latter increasingly important at high shear stress. Subsequent work led from micro- to molecular rheology in studies of the forces at play in the formation of non-covalent receptor-ligand bonds between white cells and the endothelium, important in inflammation. Since the bonds are formed under force, the force dependence of bond rupture (at the level of picoNewtons) was extensively studied for neutrophil-neutrophil and neutrophil-platelet aggregation. Fluid mechanical factors also play an important role in the localization of sites of atherosclerosis and the focal deposition of platelets resulting in thrombosis. Such sites mainly occur in regions of geometrical irregularity where vessels branch, curve and change diameter and where blood is subjected to sudden changes in velocity and/or direction. Therefore, in collaboration with Dr. Takeshi Karino, the flow behavior of red cells and platelets in such regions was studied and the connection made between the flow patterns (recirculation zones or eddies) and the increased deposition of cells on the vessel wall, as well as the formation of aggregates in regions of flow separation.