Date on Master's Thesis/Doctoral Dissertation

5-2011

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemical Engineering

Committee Chair

Berson, Robert E. (Eric)

Author's Keywords

Computational fluid dynamics; Endothelial cells; Orbital shaker; Atherosclerosis; Oscillatory shear stress; Fluid dynamic analysis

Subject

Fluid dynamics

Abstract

This work presents a novel comprehensive effort to understand the fluid dynamics within orbiting dishes and the effects of the resulting oscillating fluid flow on shear and endothelial cellular responses within the dishes. It is well documented that hemodynamic parameters, especially wall shear stress (WSS), have been shown to play important roles in altering various endothelial cellular responses, intracellular pathways and gene expression, and to have significant impacts on disease progression, such as atherosclerotic plaque development. In practice, wall shear stress (WSS) is oscillatory rather than steady due to the travelling waveform and varies across the surface of the dish at any instant in time. The first part of this effort presents a computational model which provides complete spatial and temporal resolution of oscillatory WSS over the bottom surface of an orbiting Petri dish throughout the orbital cycle. The model was reasonably well validated by the analytical solution and the results were compared to the tangential WSS magnitudes obtained using one-dimensional optical velocimetry at discreet locations on the bottom of an orbiting dish. A thorough fluid dynamic analysis was performed in the next part of this work to understand the fluid motion inside the dish by investigating the system properties that affect WSS. To identify the effects of each of those properties on WSS, a dimensional analysis study was performed which includes analyses of three dimensionless parameters - Slope ratio, Froude Number, and Stokes Number. A fourth Reynolds Number was held constant. By analyzing a range from low to high values for each of the parameters, transition points for each of the flow parameters were determined. Further the nature of WSS at different radii (20%, 40%, 60% and 80% of the maximum radius of the dish) on the bottom surface was studied as a function of combinations of various dimensionless parameters. In the last part of this study, this model was applied to understand the effects of oscillatory WSS on endothelial cellular responses, including cell proliferation, morphology, and atherogenic gene expression. Since WSS on the bottom of the dish is two-dimensional, a new directional oscillatory shear index (DOSI) was developed to quantify the directionality of oscillating shear. DOSI approached zero for bidirectional oscillatory shear of equal magnitudes near the center and approached one for unidirectional oscillatory shear near the wall, where large tangential WSS dominated a much smaller radial component. Cellular responses including cell proliferation, area, shape index, orientation, and atherogenic gene expressions at mRNA level (1-CAMl, E-Selectin, IL-6) were then correlated with different DOS I level under the same flow conditions. A comprehensive statistical analysis demonstrated that DOSI significantly affects all the responses, indicating that, in addition to shear magnitudes, directionality and the oscillatory nature of shear significantly influence cellular responses.

Download

Share

COinS