Numerical Studies of Stokes Flow in Confined Geometries

The current thesis includes two distinct projects. The first study involves the development of a novel three-dimensional Spectral Boundary Element algorithm for interfacial dynamics in Stokes flow. Our algorithm is the only available high-order/high-accuracy methodology for the problem of droplet deformation in viscous flows. By applying this algorithm to several interfacial problems, we find that our results are in excellent agreement with experimental findings, analytical predictions and previous numerical computations. The second project studies viscous flows over a protuberance on the inner wall of a solid microtube, a problem relevant to both physiological systems and microfluidic devices. The shear stress, drag and torque on the protuberance are determined as functions of the spreading angle and the relative size of the protuberance which may represent leukocytes, blood clots or endothelial cells on the microvessel wall. This study facilitates the understanding of mechano-transduction phenomena as well as cell adhesion in blood flow

Flow and interfacial dynamics in vascular vessels and microfluidics

This dissertation investigates the hemodynamic forces on biological cells adherent on vascular vessels as well as the interfacial dynamics of droplet motion in microfluidic channels. In addition, we develop a novel three-dimensional spectral boundary element algorithm for interfacial dynamics in Stokes flow. In physiological systems, the hemodynamic forces exerted on endothelial cells in vascular vessels affect the behavior of the cells via mechano-transduction. The hemodynamic forces also play a pivotal role in the adhesion of leukocytes onto the surface of blood vessels. This study investigates the relative importance and the nature of the two components of the hemodynamic force, i.e., the shear and normal force, on the cell and its vicinity. Based on computational investigation and scaling analysis, the study demonstrates that the normal force contributes significantly to the total hemodynamic force on the cell. This study points out the importance of the normal force exerted on biological cells attached to blood vessels which has been overlooked. This research may motivate experiments to identify the effects of the normal force on the functions of biological cells adhered in blood vessels. The results of the study are also applicable to the fluid forces over protuberances in microfluidic devices and porous media. For the efficient study of droplet dynamics, we have developed a novel three-dimensional high-order/high-accuracy spectral boundary element algorithm for interfacial dynamics in Stokes flow. This methodology has been employed to several interfacial problems and the results are in excellent agreement with experimental findings, analytical predictions and previous numerical computations. We also investigate the droplet motion in confined geometries which is primarily motivated by the recent development of microfluidic devices and has applications in the enhanced oil recovery, lubrication and coating processes. We consider the buoyancy-driven droplet motion along a solid wall and the pressure-driven droplet motion in a micro-channel. The influence of capillary number, Bond number and viscosity ratio on the droplet motion and deformation is investigated

Mechanics of Channel Gating of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor (nAChR) is a key molecule involved in the propagation of signals in the central nervous system and peripheral synapses. Although numerous computational and experimental studies have been performed on this receptor, the structural dynamics of the receptor underlying the gating mechanism is still unclear. To address the mechanical fundamentals of nAChR gating, both conventional molecular dynamics (CMD) and steered rotation molecular dynamics (SRMD) simulations have been conducted on the cryo-electron microscopy (cryo-EM) structure of nAChR embedded in a dipalmitoylphosphatidylcholine (DPPC) bilayer and water molecules. A 30-ns CMD simulation revealed a collective motion amongst C-loops, M1, and M2 helices. The inward movement of C-loops accompanying the shrinking of acetylcholine (ACh) binding pockets induced an inward and upward motion of the outer β-sheet composed of β9 and β10 strands, which in turn causes M1 and M2 to undergo anticlockwise motions around the pore axis. Rotational motion of the entire receptor around the pore axis and twisting motions among extracellular (EC), transmembrane (TM), and intracellular MA domains were also detected by the CMD simulation. Moreover, M2 helices undergo a local twisting motion synthesized by their bending vibration and rotation. The hinge of either twisting motion or bending vibration is located at the middle of M2, possibly the gate of the receptor. A complementary twisting-to-open motion throughout the receptor was detected by a normal mode analysis (NMA). To mimic the pulsive action of ACh binding, nonequilibrium MD simulations were performed by using the SRMD method developed in one of our laboratories. The result confirmed all the motions derived from the CMD simulation and NMA. In addition, the SRMD simulation indicated that the channel may undergo an open-close (O ↔ C) motion. The present MD simulations explore the structural dynamics of the receptor under its gating process and provide a new insight into the gating mechanism of nAChR at the atomic level

Analysis of Yarrowia lipolytica Growth, Catabolism, and Terpenoid Biosynthesis during Utilization of Lipid-derived Feedstock

This study employs biomass growth analyses and 13C-isotope tracing to investigate lipid feedstock utilization by Yarrowia lipolytica. Compared to glucose, oil-feedstock in the minimal medium increases the yeast\u27s biomass yields and cell sizes, but decreases its protein content (\u3c20% of total biomass) and enzyme abundances for product synthesis. Labeling results indicate a segregated metabolic network (the glycolysis vs. the TCA cycle) during co-catabolism of sugars (glucose or glycerol) with fatty acid substrates, which facilitates resource allocations for biosynthesis without catabolite repressions. This study has also examined the performance of a β-carotene producing strain in different growth mediums. Canola oil-containing yeast-peptone (YP) has resulted in the best β-carotene titer (121 ± 13 mg/L), two-fold higher than the glucose based YP medium. These results highlight the potential of Y. lipolytica for the valorization of waste-derived lipid feedstock

Free energy landscape for the binding process of Huperzine A to acetylcholinesterase

Drug-target residence time (t = 1/koff, where koff is the dissociation rate constant) has become an important index in discovering betteror best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, koff and activation free energy of dissociation (ΔG≠ off). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated.We applied this method to simulate the binding event of the anti-Alzheimer’s disease drug (−)−Huperzine A to its target acetylcholinesterase (AChE). The computational results are in excellent agreement with our concurrent experimental measurements. All of the predicted values of binding free energy and activation free energies of association and dissociation deviate from the experimental data only by less than 1 kcal/ mol. The method also provides atomic resolution information for the (−)−Huperzine A binding pathway, which may be useful in designing more potent AChE inhibitors. We expect thismethodology to be widely applicable to drug discovery and development

Professor State Key Laboratory of Multiphase Flow in Experimental Investigation of the Evolution and Head-On Collision of Elliptic Vortex Rings

The head-on collision process of elliptic vortex rings was experimentally investigated using flow-visualization technique as well as particle image velocimetry (PIV). Elliptic vortex rings were generated by the movement of a free moving elliptic piston-cylinder arrangement. It was found that the Q value is positive in the vortex core region while negative in the regions around the vortex core, which indicates the rotational effect is dominated in the vortex core and strain effect is dominated around the vortex core. When two elliptic vortex rings move toward each other, both rings slow down and expand in diameter direction until they merge and expand in diameter direction rapidly. The collision process of two elliptic vortex rings and the newly generated vortex structure after collision are dominated by the elliptic vortex ring with larger aspect ratio and the trajectories of vortex core almost coincide in different Reynolds numbers

A new acceleration factor for the testing of corrosion protective coating: flow-induced coating degradation,

Abstract For corrosion protective coatings that are designed to give lifetimes of protection that may extend to 50 years, valid accelerated test methods are necessary to develop improved systems and validate performance. Fluid flow over metals has long been believed to influence the corrosion process. Studies have been focused on the effects of flow rate on the corrosion of bare metals. The influence of fluid flow on the degradation of metal-protective coatings has received less attention. This paper describes a preliminary study on the influence of laminar flow on organic coatings. A Hele-Shaw cell and its associated fluid control apparatuses are incorporated into the electrochemical cell setup. The barrier properties of the coating as a function of immersion time and flow rate have been monitored by electrochemical impedance spectroscopy. We observe that the barrier properties of the coating measured electrochemically decrease exponentially with the increasing flow rate. We propose that the flowing electrolyte solution could be used in acceleration tests for the lifetime prediction of organic coatings as the acceleration of failure we have observed does not appear to change the mechanism of failure. Further analysis is proposed to validate immersion flow rate as a universal accelerating parameter for coating failure

Interface algorithm development for PHIL simulations of MMC-HVDC devices via real-time impedance matching

Power hardware-in-the-loop (PHIL) simulation combines the advantages of digital and physical simulations, which is an effective method to study and analyse modular multi-level-converter-based high-voltage direct current (MMC-HVDC) technology. For the damping impedance method (DIM) interface algorithm, a real-time impedance matching method is proposed to improve the stability and accuracy of the PHIL simulation system. The equivalent impedance between the power interface and the MMC converter station is calculated according to the voltage difference and current between them, and the equivalent impedance parameters of MMC, in both de-blocking and blocking modes, are obtained by the Thevenin equivalent models; then the information of the hardware under test impedance is used to update the DIM interface algorithm. In addition, a compensation control method for interface delay is used to reduce the system error. The excellent performance of stability and accuracy is verified by digital simulation results, which show that the proposed DIM interface algorithm is able to keep the PHIL simulation system stable under different kinds of disturbances and the maximum relative error of the active power <1.2%