Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/35052
Title: Experimentation, modeling and control of calcium dynamics in human vascular endothelial cells
Authors: CAO LINGLING
Keywords: intracellular calcium dynamics, endothelial cells, shear stress, ATP, closed-loop control, cell experiment
Issue Date: 6-Jan-2012
Source: CAO LINGLING (2012-01-06). Experimentation, modeling and control of calcium dynamics in human vascular endothelial cells. ScholarBank@NUS Repository.
Abstract: Calcium ion, as a ubiquitous second messenger found in almost all types of cells, has played an important role regulating various cellular functions. In human vascular endothelial cells (VECs), the dynamic behavior of intracellular calcium, i.e., its temporal/spatial variation, will directly affect cell proliferation, synthesis and secretion of vaso-active factors like nitric oxide (NO), and gene regulation. Therefore finding the way to encode useful information into calcium signaling process, that is to adjust the calcium dynamics via external stimuli, has become extremely meaningful. In this thesis, a framework under which the regulation of intracellular calcium dynamics could be investigated via mathematical modeling and wet lab experimentation has been constructed. A microfluidic device is fabricated for cell culture and flow loading tests. The intracellular calcium level is monitored through a fluorescent microscope simultaneously. To achieve successful intracellular calcium regulation, it is necessary to gain a comprehensive understanding of the interplay among shear stress, ATP and calcium dynamics. Based on our own experiments, three mathematical models have been built to capture shear stress-induced ATP release from VECs. The conventional proportional-integral-differential (PID) controller is employed to modulate ATP release via simulation study. By adjusting shear stress and exogenous ATP, the regulation of calcium dynamics has achieved. By feeding the system a pre-designed control command, three letters ¿N¿, "U¿ and "S¿ (representing National University of Singapore) have been generated. The feedback control is also implemented. The knowledge-based fuzzy rules are utilized to update input signals and the experimental results indicate a better tracking of letters ¿N¿, "U¿ and "S¿. Though very little of the downstream reactions triggered by such ¿N¿, "U¿ and "S¿ calcium profiles is known to us, it is believed the work presented in this thesis might open up a new scenario where engineering approaches, i.e., system and control theory, could be applicable to a biological plant at cellular and/or gene level, facilitating the biochemical reactions involved toward a beneficial direction promisingly.
URI: http://scholarbank.nus.edu.sg/handle/10635/35052
Appears in Collections:Ph.D Theses (Open)

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