Date of Award

6-2018

Degree Name

Doctor of Philosophy

Department

Chemical and Paper Engineering

First Advisor

Dr. Dewei Qi

Second Advisor

Dr. James R. Springstead

Third Advisor

Dr. Tianshu Liu

Fourth Advisor

Dr. William W. Liou

Abstract

It has been widely acknowledged that further understanding about the dynamics between blood cells and blood flow can help us gain more knowledge about the causes of diseases and discover more effective treatments. Examples of such dynamics include red blood cell (RBC, or erythrocyte) aggregation, white blood cell (WBC, or leukocyte) margination, and WBC extravasation. WBC extravasation is an important multiple-step process in the inflammatory response and therefore has drawn considerable attention over the past two decades. In this multiple-step process, a WBC undergoes at least four steps, including capture, rolling, firm adhesion, and transmigration, and each step is influenced significantly by blood flow. With the improvement of computational technology, numerical cell models, combined with the computation fluid dynamics (CFD) methods, have been widely used to simulate WBC extravasation, particularly from capture to firm adhesion.

In the earliest attempts of simulations, the WBCs were assumed to be rigid. Later experimental and numerical studies, however, indicated that deformation occurs and significantly influences the rolling of WBCs. Therefore, recent simulation studies have considered the deformability of the WBCs. Most of the current simulation studies, however, still do not consider the deformability of microvilli, which are fingerlike projections on WBC surface. In this research, we develop a more realistic simulation model, which overcomes these drawbacks. Results and methods of this study can also be extended to other research in the fields of biophysics and medical sciences, such as the mechanisms of how cancer cells spread through the bloodstream.

This study is conducted through two phases: the building of the simulation model, and the application of this model. In the first phase, the model is developed through a combination of five numerical models, which is called the immersed boundary lattice-Boltzmann lattice-spring method (IBLLM). First, the lattice Boltzmann method (LBM) is used to simulate blood flow. Second, a coarse-grained cell model (CGCM) is utilized to capture the behaviors of WBCs. Third, we also use the lattice spring model (LSM) to mimic the motion of WBC microvilli, especially in terms of their deformability. Fourth, the immersed boundary method (IBM) is used for coupling the fluid (blood flow) and the solid (blood cells), Lastly, the adhesive dynamics (AD) is adopted to simulate the formation or rupture of adhesion bonds between the WBCs and the vessel walls. Also, we develop single-GPU parallel computing implementations of the IBLLM to accelerate the computing speed of the simulations. In the second phase, we apply the simulation models to investigate the influences of bending deformation of microvilli on the process of WBC rolling adhesion and the underlying mechanisms.

This study demonstrates that the IBLLM can be accelerated by implementing a single GPU device with CUDA, resulting in a maximum increase in the computational power of 80- fold speedup. Additionally, the simulation results reveal that the flexural stiffness of microvilli and their bending deformation have a profound effect on rolling velocity. As the flexural stiffness of the microvilli decreases, their bending angles increase, resulting in an increase in the number of receptor-ligand bonds and a decrease in the rolling velocity of WBCs. The present study not only contributes to the breakthrough in the field of biophysics but also help to improve medical technologies and treatments.

Access Setting

Dissertation-Open Access

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