Blood pumped from the heart to various parts of the body is conveyed by a hierarchy of blood vessels. This vascular system supplies oxygen nutrients to cells in the body and removes carbon dioxide and metabolic waste. The terminal blood vessels are capillaries, and this is where gas and nutrient exchange with surrounding tissue takes place. Demand for oxygen and nutrients varies with time in specific tissues. For example, cerebral neurons demand more oxygen during increased cognitive activities. Each organ and tissue is able to regulate its blood supply on demand. Blood flow regulation at the capillary level is known as autoregulation, and it involves dilation and contraction of vessels triggered by smooth muscle cells (SMCs) in the pre-capillary vessel wall. Autoregulation allows the capillaries to maintain constant blood flow rates despite sudden changes in pressure. Loss of autoregulation is associated with many pathological conditions, including dementia and coronary disease. Compliance of blood vessels is the key to the process. Red blood cells (RBCs) are extremely flexible; their motion through capillaries influences overall blood flow and pressure distributions, which in turn affect activation of pressure-sensitive SMCs. This project will develop a computational model of autoregulation of blood flow by combining RBC deformation, SMC activation, and vessel compliance. The model will provide a detailed understanding of the critical pathways that cause loss of autoregulation and its effects in various diseases such as dementia, stroke, heart disease, kidney failure. The project will involve mentoring graduate and undergraduate students in research, and will engage high-school students through a summer research program.
This project will develop a high-fidelity, three-dimensional, multiscale, multiphysics, fluid-structure interaction (FSI)-based computational model of autoregulation of blood flow in physiologically realistic vascular networks. It will integrate a coarse-grain bio-electro-chemical model for calcium ion-mediated active contractile stress generation in SMCs, finite-strain viscoelastic model for the dynamic response of the blood vessel walls, large deformation of flowing RBCs in suspension, and Immersed Boundary methods to couple the fluid flow with deforming interfaces. The influence of vessel compliance on RBC deformation and distribution, and the role of RBC rheology on vessel deformation will be analyzed quantitatively. The apparent viscosity of blood in compliant vessels, and the effects of vessel compliance on RBC partitioning at vascular bifurcations will also be addressed. Finally, the role of active contraction on the distribution of RBCs in a vascular network, and the role of RBC distribution on active contraction will be studied.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
