Bulletin of the American Physical Society
69th Annual Meeting of the APS Division of Fluid Dynamics
Volume 61, Number 20
Sunday–Tuesday, November 20–22, 2016; Portland, Oregon
Session A20: Bio: Proteins and Cells |
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Chair: Jin Liu, Washington State University Room: D137-138 |
Sunday, November 20, 2016 8:00AM - 8:13AM |
A20.00001: Coarse-grained Simulations of Sugar Transport and Conformational Changes of Lactose Permease Jin Liu, S M Yead Jewel, Prashanta Dutta \textit{Escherichia coli} lactose permease (LacY) actively transports lactose and other galactosides across cell membranes through lactose/H$^{\mathrm{+}}$ symport process. Lactose/H$^{\mathrm{+}}$ symport is a highly complex process that involves sugar translocation, H$^{\mathrm{+}}$ transfer, as well as large-scale protein conformational changes. The complete picture of lactose/H$^{\mathrm{+}}$ symport is largely unclear due to the complexity and multiscale nature of the process. In this work, we develop the force field for sugar molecules compatible with PACE, a hybrid and coarse-grained force field that couples the united-atom protein models with the coarse-grained MARTINI water/lipid. After validation, we implement the new force field to investigate the transport of a $\beta $-D-galactopyranosyl-1-thio-$\beta $-D-galactopyranoside (TDG) molecule across a wild-type LacY during lactose/H$^{\mathrm{+}}$ symport process. Results show that the local interactions between TDG and LacY at the binding pocket are consistent with the X-ray experiment. Protonation of Glu325 stabilizes the TDG and inward-facing conformation of LacY. Protonation of Glu269 induces a dramatic protein structural reorganization and causes the expulsion of TDG from LacY to both sides of the membrane. The structural changes occur primarily in the N-terminal domain of LacY. [Preview Abstract] |
Sunday, November 20, 2016 8:13AM - 8:26AM |
A20.00002: Computational Modeling and Simulations of Bioparticle Internalization Through Clathrin-mediated Endocytosis Hua Deng, Prashanta Dutta, Jin Liu Clathrin-mediated endocytosis (CME) is one of the most important endocytic pathways for the internalization of bioparticles at lipid membrane of cells, which plays crucial roles in fundamental understanding of viral infections and interacellular/transcelluar targeted drug delivery. During CME, highly dynamic clathrin-coated pit (CCP), formed by the growth of ordered clathrin lattices, is the key scaffolding component that drives the deformation of plasma membrane. Experimental studies have shown that CCP alone can provide sufficient membrane curvature for facilitating membrane invagination. However, currently there is no computational model that could couple cargo receptor binding with membrane invagination process, nor simulations of the dynamic growing process of CCP. We develop a stochastic computational model for the clathrin-mediated endocytosis based on Metropolis Monte Carlo simulations. In our model, the energetic costs of bending membrane and CCP are linked with antigen-antibody interactions. The assembly of clathrin lattices is a dynamic process that correlates with antigen-antibody bond formation. This model helps study the membrane deformation and the effects of CCP during functionalized bioparticles internalization through CME. [Preview Abstract] |
Sunday, November 20, 2016 8:26AM - 8:39AM |
A20.00003: Modeling of Nutrient Transport and the Onset of Hypoxia in a Microfluidic Cell Culture Environment Adnan Morshed, Prashanta Dutta Transport of essential nutrients such as oxygen and ascorbate plays a critical role in dictating tumor growth. For example, hypoxia, the depletion of intracellular oxygen levels below 6{\%}, initiates major changes in cellular dynamics causing tumor cell survival. The intercapillary distance (distance between blood vessels) across a colony of growing tumor cells and the flow around the colony are important factors for the initiation of hypoxia. In this study, the dynamics of intracellular species inside a colony of tumor cells are investigated by varying the flow and unsteady permeation in a microfluidic cell culture device. The oxygen transport across the cell membrane is modeled through diffusion, while ascorbate transport from plasma is addressed by a concentration dependent uptake model. Our model shows that the onset of hypoxia is possible in HeLa cell within the first minute of total extracellular oxygen deprivation. This eventually leads to anoxia inside the cell block representing the development of a necrotic core that maintains a dynamic balance with growing cells and scarce supply. Results also indicate that the intercapillary distance and flow rate of nutrients can alter this balance, which has implications in the progression of hypoxic response. [Preview Abstract] |
Sunday, November 20, 2016 8:39AM - 8:52AM |
A20.00004: Computational Studies of Drug Release, Transport and Absorption in the Human Intestines Farhad Behafarid, J. G. Brasseur, G. Vijayakumar, B. jayaraman, Y. Wang Following disintegration of a drug tablet, a cloud of particles 10-200 $\mu $m in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the ``fasting'' vs. ``fed'' motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local `quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. \textit{Supported by FDA.} [Preview Abstract] |
Sunday, November 20, 2016 8:52AM - 9:05AM |
A20.00005: Transport of Brownian spheroidal nanoparticles in near-wall vascular flows for cancer therapy Tiras Y. Lin, Preyas N. Shah, Bryan R. Smith, Eric S.G. Shaqfeh The microenvironment local to a tumor is characterized by a leaky vasculature induced by angiogenesis from tumor growth. Small pores form in the blood vessel walls, and these pores provide a pathway for cancer-ameliorating nanoparticle drug carriers. Using both simulations and microfluidics experiments, we investigate the extravasation of nanoparticles through pores. Using Brownian dynamics simulations, we evolve the stochastic equations for both point particles and finite-size spheroids of varying aspect ratio. We investigate the effect of wall shear flow and pore suction flow (Sampson flow) on the extravasation process. We consider pores of two types: physiologically relevant short pores with a length equal to the particle size and long pores which are relevant to diffusion through membranes. Additionally, we perform microfluidics experiments in which the extravasation rates of various nanoparticles tagged with fluorescent dye through pores are measured. In particular, using fluorometry we measure the flux of nanoparticles across a track-etched membrane, which separates two chambers. Our preliminary results indicate that the flux measured from experiment agrees reasonably with the simulations done with long pores, and we discuss the effect of pore length on extravasation. [Preview Abstract] |
Sunday, November 20, 2016 9:05AM - 9:18AM |
A20.00006: Numerical analysis of cell adhesion in capillary flow Naoki Takeishi, Yohsuke Imai, Shunichi Ishida, Toshihiro Omori, Roger Kamm, Takuji Ishikawa Numerical simulation of cell adhesion was performed for capillaries whose diameter is comparable to or smaller than that of the cell. Despite a lot of works about leukocyte and tumor cell rolling, cell motion in capillaries has remained unclear. The solid and fluid mechanics of a cell in flow was coupled with a slip bond model of ligand-receptor interactions. When the size of a capillary was reduced, the cell always transitioned to “bullet-like” motion, with a consequent decrease in the velocity of the cell. A state diagram is obtained for various values of capillary diameter and receptor density. According to our numerical results, bullet motion enables firm adhesion of a cell to the capillary wall even for a weak ligand-receptor binding. We also quantified effects of various parameters, including the dissociation rate constant, the spring constant, and the reactive compliance on the characteristics of cell motion. Our results suggest that even under the interaction between PSGL-1 and P-selectin, which is mainly responsible for leukocyte rolling, a cell is able to show firm adhesion in a small capillary. These findings may help in understanding such phenomena as leukocyte plugging and cancer metastasis. [Preview Abstract] |
Sunday, November 20, 2016 9:18AM - 9:31AM |
A20.00007: Exercise, Insulin Absorption Rates, and Artificial Pancreas Control Spencer Frank, Ling Hinshaw, Rita Basu, Ananda Basu, Andrew J. Szeri Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected -- usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches. [Preview Abstract] |
Sunday, November 20, 2016 9:31AM - 9:44AM |
A20.00008: Study of Microfluidic System for Mechanical Property Measurement of Fluid-cell Interface Ji Young Moon, Jung Shin Lee, Se Bin Choi, Hong Min Yoon, Roger I. Tanner, Joon Sang Lee The system for measuring the mechanical properties of active cell is studied through an integrated microfluidic system for cell separation, alignment and measurement of mechanical properties. A highly efficient lattice Boltzmann method (LBM) was employed to optimize the micro-fluidic system to investigate the interrelations between mechanical properties and various surrounding fluid ingredients which are difficult to observe using current experimental techniques. A combination model of the three dimensional LBM and the immersed boundary method (IBM) were used to simulate these systems. The LBM was used to determine incompressible fluid flow with a regular Eulerian grid. The IBM was used to solve the deformation of cells and matrix fluid interaction with a Lagrangian grid. Highly non-linear results such as cell-cell interactions, fluid-cell interactions, and optical force-cell interactions is studied. [Preview Abstract] |
Sunday, November 20, 2016 9:44AM - 9:57AM |
A20.00009: Human endothelial cell responses to cardiovascular inspired pulsatile shear stress Matthew Watson, Lauren Baugh, Lauren Black III, Erica Kemmerling It is well established that hemodynamic shear stress regulates blood vessel structure and the development of vascular pathology. This process can be studied via in vitro models of endothelial cell responses to pulsatile shear stress. In this study, a macro-scale cone and plate viscometer was designed to mimic various shear stress waveforms found in the body and apply these stresses to human endothelial cells. The device was actuated by a PID-controlled DC gear-motor. Cells were exposed to 24 hours of pulsatile shear and then imaged and stained to track their morphology and secretions. These measurements were compared with control groups of cells exposed to constant shear and no shear. The results showed that flow pulsatility influenced levels of secreted proteins such as VE-cadherin and neuroregulin IHC. Cell morphology was also influenced by flow pulsatility; in general cells exposed to pulsatile shear stress developed a higher aspect ratio than cells exposed to no flow but a lower aspect ratio than cells exposed to steady flow. [Preview Abstract] |
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