Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Biomedical Engineering

Supervisor

Jun Yang

Abstract

Microscale technologies create great opportunities for biologists to unveil cellular or molecular mechanisms of complex biological processes. Advanced measuring techniques, like atomic force microscope (AFM), allow detecting and controlling biological samples at high spatial and temporal resolution. Further integration with microsystems, such as microfluidic platforms, gives the ability to get detailed insight into basic biological phenomena. Highly integrated microdevices show great promise for biomedical research and potential clinical applications.

It is hypothesized that biomechanical factors play a significant role in the development of vascular diseases like atherosclerosis. To explore effects of biomechanical and biochemical stimuli on endothelial cells (ECs), AFM, which allows measurements of living cells, was utilized. Due to the heterogeneity of cells, standard characterization methods for mechanical properties of cells are still lacking. Therefore, a new quantitative method was developed for evaluation of cell elasticity correlating with cell morphology in this study. Moreover, cells are intrinsically viscoelastic materials revealed by stress relaxation measurements. A mechanically distinct bilayer model was proposed to discover the mechanical behaviour of cell components. Based on the elasticity characterization method and the stress relaxation model, the effect of cholesterol content on the mechanical response of ECs was examined, focusing on the behaviour of plasma membrane.

To mimic physiological conditions more closely for in vitro settings, a mask-free, highly integrated, low cost and time effective method was developed to rapidly fabricate a prototype of microfluidic cell culture system (MCCS). To better understand cell-cell interaction in circulatory systems like MCCS, a theoretical study of evaluating intercellular forces was also performed. Based on MCCS and microvalve technique, a novel bio-inspired and cell-based system was developed to simulate the formation of atherosclerosis plaque. Biomechanical properties of ECs, hemodynamic effects, cell rolling and adhesion events were investigated under this pathological model. The devices can be leveraged for potential applicability to biological research and clinical tests such as drug screening.

This research project has led to a better understanding of the underlying mechanisms of atherosclerosis and mechanical behaviours of ECs, as well as the development of AFM-based models that will be useful in determining cellular mechanical properties.


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