Dynamics and distribution of immunoglobolin E receptors : a dialog between experiment and theory

This dissertation explores the dynamics and distribution of immunoglobulin E receptors (FceRI) on mast cells by drawing on the techniques of experimental and theoretical physics. The motivation for these investigations is provided by a considerable interest in the transmembrane signaling mechanisms of immunoreceptors, especially when triggered with membrane-bound ligands. Experimental investigations quantify the spatiotemporal dynamics of the redistribution of FceRI due to membrane-bound monovalent ligands, using total internal reflection fluorescence microscopy and single-particle tracking. When mast cells contact such substrates, receptor clusters form at cell-substrate contact points. The initial rate of accumulation of receptors into these contact points or cell protrusions is consistent with diffusion-limited trapping. Over longer timescales (\u3e10 s), individual clusters move with both diffusive and directed motion components and eventually coalesce to form a large central receptor patch surrounded by a receptor cluster depletion zone. Detailed analysis of single-particle trajectories show that receptors maintain their diffusivity when confined within receptor clusters, and increase their diffusivity (above that of monomeric unliganded FceRI) in central patches. To study the kinetics of central patch formation, a new coalescence theory described by a melding process, which is not instantaneous, was developed. In these theoretical investigations, the difficult problem of moving boundaries is encountered. To handle the complexity, which stems from boundary growth due to particle melding, the study is divided into three parts. The first is about stationary trapping problems investigated by the standard defect technique, and the second is about a validity study of an adiabatic approximation for moving boundaries. In the last part of this dissertation, a new coalescence theory is developed, which is based on a completely self-consistent approach. Here, the time dependence of the moving boundary is not prescribed but obtained through feedback. Comparison of experiment and theory shows that observed biological cluster coalescence is delayed at early times and occurs at a faster rate at later times than predicted by a simple theory. The incompatibility at early times is addressed by a generalization of the theory to incorporate a time-dependent melding process by a memory concept, which quantitatively explains the observed delay

Convergence of the tamed-Euler-Maruyama method for SDEs with discontinuous and polynomially growing drift

Numerical methods for SDEs with irregular coefficients are intensively studied in the literature, with different types of irregularities usually being attacked separately. In this paper we combine two different types of irregularities: polynomially growing drift coefficients and discontinuous drift coefficients. For SDEs that suffer from both irregularities we prove strong convergence of order $1/2$ of the tamed-Euler-Maruyama scheme from [Hutzenthaler, M., Jentzen, A., and Kloeden, P. E., The Annals of Applied Probability, 22(4):1611-1641, 2012]

Effect of D2O on vesicle motion in RBL-2H3 cells: Data set 7

<p>TIRF microscopy at 20 frames/s of diI labeled RBL-2H3 cells. Data sets are .lif imaging files collected with micromanager. Here, cells were cultured in 15 moles/L deuterium oxide and treated with 100 μM colchicine for 45 min before imaging.</p

Effect of D2O on vesicle motion in RBL-2H3 cells: Data set 3

<p>TIRF microscopy at 20 frames/s of diI labeled RBL-2H3 cells. Data sets are .lif imaging files collected with micromanager. Here, cells were cultured in 0 moles/L deuterium oxide.</p

RBL-2H3 Mast Cell Receptor Dynamics in the Immunological Synapse

The RBL-2H3 mast cell immunological synapse dynamics is often simulated with reaction&ndash;diffusion and Fokker&ndash;Planck equations. The equations focus on how the cell synapse captures receptors following an immune response, where the receptor capture at the immunological site appears to be a delayed process. This article investigates the physical nature and mathematics behind such time-dependent delays. Using signal processing methods, convolution and cross-correlation-type delay capture simulations give a &chi;-squared range of 22 to 60, in good agreement with experimental results. The cell polarization event is offered as a possible explanation for these capture delays, where polarizing rates measure how fast the cell polarization event occurs. In the case of RBL-2H3 mast cells, polarization appears to be associated with cytoskeletal rearrangement; thus, both cytoskeletal and diffusional components are considered. From these simulations, a maximum polarizing rate ranging from 0.0057 s&minus;2 to 0.031 s&minus;2 is obtained. These results indicate that RBL-2H3 mast cells possess both temporal and spatial memory, and cell polarization is possibly linked to a Turing-type pattern formation

A Model for the Spread of Infectious Diseases with Application to COVID-19

Given the present pandemic caused by the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 virus, the authors tried fitting existing models for the daily loss of lives. Based on data reported by Worldometers on the initial stages (first wave) of the pandemic for countries acquiring the disease, the authors observed that the logarithmic rendering of their data hinted the response of a first-order process to a step function input, which may be modeled by a three-parameters function, as described in this paper. This model was compared against other similar, log(N)-class of models that are non-compartmental type (such as the susceptible, infected, and removed, or SIR models), obtaining good fit and statistical comparison results, where N denotes the cumulative number of daily presumed deaths. This simple first-order response model can also be applied to bacterial and other biological growth phenomena. Here we describe the model, the numerical methods utilized for its application to actual pandemic data, and the statistical comparisons with other models which shows that our simple model is comparatively outstanding, given its simplicity. While researching the models available, the authors found other functions that can also be applied, with extra parameters, to be described in follow-on articles

Use of Magnetic Nanoparticles as In Situ Mucus Property Probe

Magnetic nanoparticles (MNPs) are unique in their abilities to penetrate and interact with a wide range of liquid media. Because of their magnetic properties, MNPs can be directed to any area of interest, and interact with core structures deep inside the medium which is normally inaccessible. In this report, we investigate the behavior of MNPs in a specific biological fluid, namely in a mucus layer of air–liquid interface cultured primary normal human tracheobronchial epithelial cells. Using Fokker–Planck algorithm simulations and observing the behavior of MNPs from prior experiments, we found MNPs that are initially less than 100 nm in size, to aggregate into sizes of ~50 μm and to deviate from the expected Fokker–Planck distribution due to the mucus structure. Based on our analysis, human tracheobronchial epithelial (NHTE) cell mucus viscosity ranges from 15 Pa·s to 150 Pa·s. The results not only confirm the possible use of MNPs as a means for medical drug delivery but also underline important consequences of MNP surface modifications

Imaging Membrane Curvature inside a FcεRI-Centric Synapse in RBL-2H3 Cells Using TIRF Microscopy with Polarized Excitation

Total internal reflection fluorescence microscopy with polarized excitation (P-TIRF) can be used to image nanoscale curvature phenomena in live cells. We used P-TIRF to visualize rat basophilic leukemia cells (RBL-2H3 cells) primed with fluorescent anti-dinitrophenyl (anti-DNP) immunoglobulin E (IgE) coming into contact with a supported lipid bilayer containing mobile, monovalent DNP, modeling an immunological synapse. The spatial relationship of the IgE-bound high affinity IgE receptor (Fc&epsilon;RI) to the ratio image of P-polarized excitation and S-polarized excitation was analyzed. These studies help correlate the dynamics of cell surface molecules with the mechanical properties of the plasma membrane during synapse formation

Effects of deuterium oxide on cell growth and vesicle speed in RBL-2H3 cells

For the first time we show the effects of deuterium oxide on cell growth and vesicle transport in rat basophilic leukemia (RBL-2H3) cells. RBL-2H3 cells cultured with 15 moles/L deuterium showed decreased cell growth which was attributed to cells not doubling their DNA content. Experimental observations also showed an increase in vesicle speed for cells cultured in deuterium oxide. This increase in vesicle speed was not observed in deuterium oxide cultures treated with a microtubule-destabilizing drug, suggesting that deuterium oxide affects microtubule-dependent vesicle transport