Computational Modeling of Platelet Aggregation and Coagulation and Development of Software for Biofluid Dynamics Problems

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Fogelson9805518 The investigator undertakes modeling and computationalsimulation of platelet aggregation and coagulation. These arethe components of normal blood clotting and of thelife-threatening blood clots associated with vascular disease andwith the use of cardiovascular prostheses. The investigator andcoworkers continue to explore and refine their models of plateletaggregation in small and large diameter vessels; continuedevelopment of models of coagulation including the effects offlow, transport, and surface reactions; and integrate theplatelet aggregation and coagulation models to form a morecomprehensive model of the hemostatic and thrombotic processes.These models use coupled systems of nonlinear partial andordinary differential equations to describe interactions betweenthe blood's fluid dynamics, the transport of platelets andchemicals in the blood plasma, the mechanics and chemistry ofdeveloping aggregates, and the solution-phase and surface-boundbiochemistry of the coagulation process. The models presentsubstantial computational challenges that require development anduse of state-of-the-art numerical methods for their solution.These include immersed boundary methods for fluid-materialinteractions, high-resolution finite-difference methods combinedwith Fourier-collocation spectral methods, immersed-interfacemethods for handling transport in regions of complex geometry,and parallel computation. This work involves extensivecomparisons between computational results and laboratoryexperiments and is aided by collaboration with leading experts onflow and thrombosis. The proposal is also concerned withdeveloping state-of-the-art parallel computational methods forsimulating biofluid dynamic flows like those involved inaggregation and coagulation, and with including thesecomputational tools in a powerful and easy-to-use problem solvingenvironment that facilitates solving a wide range of complexbiofluid dynamic problems. Thrombosis, which is the formation of blood clots withinvessels of the circulatory system, is the proximal cause of mostheart attacks and of other severe cardiovascular problems such asischemia and angina. It is also a major problem associated withthe use of blood-contacting prostheses such as mechanical heartvalves. The process by which these blood clots form is verycomplex and involves many dynamic, sometimes competing, sometimesmutually-reinforcing, biophysical and biochemical processes. Amajor part of this project involves developing powerfulmathematical and computational tools for studying this complexprocess, and using these tools to probe the factors that effectthe location, extent, and speed of formation of thrombi.Computational modeling complements traditional experimentalapproaches and provides a way to simulate complex dynamic events,like the dynamic interactions among fluid, blood cells, clottingfactors, and blood vessel or prosthesis surface that lead tothrombosis, that are beyond the reach of current laboratorytechniques. Such simulations can give new insights into thebasic mechanisms that control this important biological process,and can ultimately help in the more rational design oftherapeutic interventions and prosthetic devices. Many otherchallenging biological and biomedical flow problems have featuresin common with that of simulating thrombosis, and so thestate-of-the-art parallel computational methods developed forthis project potentially have wide-spread application to problemsimportant to basic science, health care, and biotechnology. Tohelp realize this potential the investigators develop anddisseminate an easy-to-use software package that facilitatesusing these computational methods to set up and carry outsimulations of important biofluid dynamics problems.