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Date of Award
2020
Document Type
Campus Access Master's Thesis
Degree Name
Master of Science in Biomedical Engineering (MS)
Administrative Home Department
Department of Biomedical Engineering
Advisor 1
Sangyoon Han
Committee Member 1
Smitha Rao
Committee Member 2
Chang Kyoung Choi
Abstract
A parallel plate flow chamber-based flow system is a flow system that allows for microscopic observation of the endothelial cell (EC) monolayer behavior in response to different flow conditions in a controlled manner. ECs’ flow response has been a critical factor that determines atherosclerotic legion formation at specific locations of arteries with disturbed shear. While many flow systems have been developed for such behaviors, however, they have lacked a modality to measure mechanical forces exerted by the ECs in response to the onset of shear flow, which is an important linkage in mechano-transduction cascade in the ECs. In this thesis, a flow system based on parallel plate flow chamber is developed with addition of a force sensor, referred to as traction force microscopy (TFM), on the chamber bottom surface. The flow chamber was designed, and manufactured 3D-printed holder and polydimethylsiloxane (PDMS)-based internal flow channel that ensures leakage-proof design. Computational fluid dynamics simulation was performed to ensure generation of laminar flow and uniform shear stress inside the flow channel. Using the assembled chamber and peristaltic pump-based flow system, a pilot experiment was performed to test a hypothesis that the shear stress generated on the luminal surface of the ECs is transferred to the cell-ECM adhesion site via cell cytoskeleton. The traction force was measured via TFM in real-time. Effect of shear flow on ECs showed an increase in force as an immediate response to the onset of the flow. Short time (30 minutes) flow results indicated that force increases overtime under a laminar shear stress of 1.0 Pa. Other key factors were identified such as high shear flow, cell confluency and phototoxicity, which can greatly influence the traction force transmission.
Recommended Citation
Chandurkar, Mohanish, "DEVELOPMENT AND VALIDATION OF THE FLOW CHAMBER FOR SHEAR FLOW MECHANOTRANSMISSION STUDIES", Campus Access Master's Thesis, Michigan Technological University, 2020.