关键词:
Mechanical engineering
Biomechanics
Biophysics
摘要:
Numerous fundamental biomedical studies were performed on red blood cells (RBCs) in the 1960s through the 1980s, which combined physical and engineering principles with biology [31, 55, 66, 75, 84, 155]. However, since then many technological advancements have aided in experimentation at faster time and smaller spatial scales. In addition, more recent studies now integrate signaling cascades and molecular processes. These advancements, in combination with new ideas and earlier work in the RBC field, allow for a second look into RBCs and how they participate in flow. RBC experiments incorporating physical dynamics and biochemical processes at multiple spatial and time scales will increase our understanding of the physiological roles of RBCs, and provides new perspective on vascular disease mechanisms. This thesis explores the interaction between RBCs and flow, in both the chemical and physical domains. Chapter 1 is a review of the current literature on RBC deformation, dynamics, and ATP release from RBCs at the cellular and subcellular level. Chapter 2 is a study on the role of diamide, which is commonly used as a RBC stiffening agent. However, discrepancies in the literature surrounding diamide's effect on the deformation were still present. In Chapter 3 microfluidics, rheology, and a bioluminescent detection method are employed to elucidate the links between cell dynamics, viscosity, and ATP release. Important findings include the recognition that shear thinning is not due to cellular deformation as previously believed, but rather is due to the RBC tumbling-to-tanktreading transition. Additionally, new insight into the ATP release cascade is developed. In Chapter 4, the role of membrane cholesterol in reducing deformation and ATP release is revealed. In addition, simvastatin, a popular drug for treating hypercholesterolemia, is shown to increase ATP release and deformability of RBCs. In Chapter 5, ecto-ATPase activity on RBC membranes is highlighted while investiga