Type

Text

Type

Dissertation

Advisor

Deng, Yuefan | Zhu, Wei | Bluestein, Danny | Einav, Shmuel.

Date

2015-12-01

Keywords

Applied mathematics

Department

Department of Applied Mathematics and Statistics.

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/76282

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Mechanical Heart Valves (MHV) provides life-saving solutions to patients suffering from cardiovascular diseases. But these devices are often plagued by non-physiological flow patterns resulting in increased shear stress conditions. This leads to platelet damage, a precursor of thromboembolism, thus impeding the device usability and demanding lifelong anticoagulation treatments. While the flow and stresses are in the micron level, the platelet behavior is at the nm level, thus presenting a major computational challenge for simulating this multiscale multi-physics modeling problem. This dissertation focuses on using parallel computers to develop a computational framework based on n-particle simulations, defined by Coarse Grained Molecular Dynamics (CGMD) for platelets and Dissipative Particle Dynamics (DPD) for fluids. First, the problem of developing a three-dimensional (3D) platelet model to characterize the filopodia formation observed during activation is considered. This CGMD particle-based model can deform to emulate the complex shape change and filopodia formation that platelets undergo during activation. The model represents the phenomenological functions of the three platelet cellular zones; peripheral, structural and organelle, by bonded and non-bonded particles. By exploring the parameter space of this CGMD model, successful simulations of the dynamics of varied filopodia formation on platelets is demonstrated. Second, a quantitative model for platelet morphological change that considers filopodial dynamics, circularity of the central body and average filopod number is presented. Derived from the logistic equation, the morphological change is expressed as a mathematical function of mechanical shear stress and exposure time and this quantitative model for the overall platelet morphology is corroborated with in vitro experiments. The model for the first time enables a quantitative analysis of platelet morphology during early stages of activation and offers insights into the underlying effects of mechanical shear stresses over time on platelet morphology. | 115 pages

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