Temporally and spatially resolved quantification of hemodynamic forces and endothelial mechanics

Authors

Lori M. Lambert, University of Nebraska-LincolnFollow

Date of this Version

Spring 5-2016

Comments

A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Mechanical Engineering & Applied Mechanics (Fluid Mechanics), Under the Supervision of Professor Timothy Wei. Lincoln, Nebraska: May, 2016

Copyright (c) 2016 Lori M. Lambert

Abstract

The endothelium is a thin layer of endothelial cells that line the interior surface of an artery. Due to their direct contact with blood flow, endothelial cells experience varying hemodynamic forces and respond to these forces by altering their morphology. When plaque and other substances accumulate in the walls of arteries, i.e., atherosclerosis, endothelial cells have abnormal responses to blood flow. Studying atherosclerosis progression is, therefore, a two-fold investigation into 1) the hemodynamic forces that cause endothelial responses, and 2) the biological and mechanical responses of endothelial cells. The ultimate goal of this study was to develop an experimental method that was able to temporally and spatially quantify hemodynamic forces and endothelial mechanics.

The current study cultured bovine aortic endothelial cell monolayers in microchannels and used micro-particle tracking velocimetry (µPTV) techniques and fluid mechanics principles to quantify fluid forces and cell morphology for monolayers subjected to steady shear rates of 5, 10 and 20 dyne/cm². Cell topography, shear stress, and pressure distributions were calculated from sets of velocity fields made in planes parallel to the microchannel wall. For each experiment, measurements were made in three-hour intervals for 18 hours. Endothelial cell conditions varied between normal and necrotic and the cell culture surface varied between untreated glass and fibronectin-coated glass. This study demonstrated the ability to make in-situ quantifications of fluid forces and endothelial mechanics using µPTV techniques and fluid mechanics principles. It was found that there is a three-dimensional change in cell morphology as a result of applied shear stress. In addition, cell morphology is directly related to local variations in fluid loading, i.e., shear stress and pressure.

Adviser: Timothy Wei