Bulletin of the American Physical Society
APS March Meeting 2011
Volume 56, Number 1
Monday–Friday, March 21–25, 2011; Dallas, Texas
Session D39: Physics of Physiological Systems |
Hide Abstracts |
Sponsoring Units: DBP Chair: Wolfgang Losert, University of Maryland Room: A124/127 |
Monday, March 21, 2011 2:30PM - 2:42PM |
D39.00001: Axonal Transport and Morphology: How Myelination gets Nerves into Shape Peter Jung, Peng Zhao, Paula Monsma, Tony Brown The local caliber of mature axons is largely determined by neurofilament (NF) content. The axoskeleton, mainly consisting of NFs, however, is dynamic. NFs are assembled in the cell body and are transported by molecular motors on microtubule tracks along the axon at a slow rate of fractions of mm per day. We combine live cell fluorescent imaging techniques to access NF transport in myelinated and non-myelinated segments of axons with computational modeling of the active NF flow to show that a), myelination locally slows NF transport rates by regulating duty ratios and b), that the predicted increase in axon caliber agrees well with experiments. This study, for the first time, links NF kinetics directly to axonal morphology, providing a novel conceptual framework for the physical understanding of processes leading to the formation of axonal structures such as the ``Nodes of Ranvier'' as well as abnormal axonal swellings associated with neurodegenerative diseases like Amyotrophic lateral sclerosis (ALS). [Preview Abstract] |
Monday, March 21, 2011 2:42PM - 2:54PM |
D39.00002: Experimental evaluation of biophysical neurite growth models Zachary Wissner-Gross, Mark Scott, David Ku, Priya Ramaswamy, Mehmet Yanik During nervous system development, neurons exhibit complex growth dynamics, as several neurites compete to become each neuron's axon. Numerous mathematical and biophysical models have been proposed to explain this competition, but these models remain experimentally unverified. Large-scale and repeatable measurements of neurite dynamics are difficult to perform, since neurons have varying numbers of neurites, which themselves have complex morphologies. To overcome these challenges using a minimal number of primary neurons, we generated repeatable neuronal morphologies by laser-patterning micron-wide stripes of adhesive proteins on an otherwise highly non-adherent substrate. Upon analyzing thousands of time-lapse measurements, we observed three key neuronal behaviors: total neurite growth accelerated until neurons polarized, immature neurites competed even at very short lengths, and neuronal polarity underwent an apparent phase transition as the neurites grew beyond a critical length. Proposed biophysical neurite growth models agreed only partially with our experimental observations, and simple yet specific modifications significantly improved these models. The protein patterning and high-content analyses presented here could also be employed for studying other structural or biomechanical cellular phenomena. [Preview Abstract] |
Monday, March 21, 2011 2:54PM - 3:06PM |
D39.00003: Deep Brain Stimulation using Magnetic Fields David Jiles, Paul Williams, Lawrence Crowther New applications for transcranial magnetic stimulation are developing rapidly for both diagnostic and therapeutic purposes. Therefore so is the demand for improved performance, particularly in terms of their ability to stimulate deeper regions of the brain and to do so selectively. The coil designs that are used presently are limited in their ability to stimulate the brain at depth and with high spatial focality. Consequently, any improvement in coil performance would have a significant impact in extending the usefulness of TMS in both clinical applications and academic research studies. New and improved coil designs have then been developed, modeled and tested as a result of this work. A large magnetizing coil, 300mm in diameter and compatible with a commercial TMS system has been constructed to determine its feasibility for use as a deep brain stimulator. The results of this work have suggested directions that could be pursued in order to further improve the coil designs. [Preview Abstract] |
Monday, March 21, 2011 3:06PM - 3:18PM |
D39.00004: Growth of Necrotic Cores in Vulnerable Plaque Pak-Wing Fok Plaques are fatty deposits that grow mainly in arteries and develop as a result of a chronic inflammatory response. Plaques are called \textit{vulnerable} when they are prone to mechanical rupture. Vulnerable Plaques (VPs) are characterized by lipid-rich, necrotic cores that are heavily infiltrated with macrophages. The rupture of VPs releases thrombogenic agents into the bloodstream, usually resulting in myocardial infarctions. We propose a quantitative model to predict the development of a plaque's necrotic core. By solving coupled reaction-diffusion equations for macrophages and dead cells, we explore the joint effects of hypoxic cell death and chemo-attraction to Ox-LDL, a molecule that is strongly linked to atherosclerosis. Our model predicts cores that have approximately the right size and shape. Normal mode analysis and subsequent calculation of the smallest eigenvalues allow us to compute the times required for the system to reach its steady state. This study allows us to make quantitative predictions for how quickly vulnerable plaques develop and how their growth depends on system parameters such as chemotactic coefficients and cell death rates. [Preview Abstract] |
Monday, March 21, 2011 3:18PM - 3:30PM |
D39.00005: Understanding cellular architecture in cancer cells Simone Bianco, Chao Tang Understanding the development of cancer is an important goal for today's science. The morphology of cellular organelles, such as the nucleus, the nucleoli and the mitochondria, which is referred to as cellular architecture or cytoarchitecture, is an important indicator of the state of the cell. In particular, there are striking difference between the cellular architecture of a healthy cell versus a cancer cell. In this work we present a dynamical model for the evolution of organelles morphology in cancer cells. Using a dynamical systems approach, we describe the evolution of a cell on its way to cancer as a trajectory in a multidimensional morphology state. The results provided by this work may increase our insight on the mechanism of tumorigenesis and help build new therapeutic strategies. [Preview Abstract] |
Monday, March 21, 2011 3:30PM - 3:42PM |
D39.00006: A two-scale model for correlation between B cell VDJ usage in zebrafish Keyao Pan, Michael Deem The zebrafish (Danio rerio) is one of the model animals for study of immunology. The dynamics of the adaptive immune system in zebrafish is similar to that in higher animals. In this work, we built a two-scale model to simulate the dynamics of B cells in primary and secondary immune reactions in zebrafish and to explain the reported correlation between VDJ usage of B cell repertoires in distinct zebrafish. The first scale of the model consists of a generalized NK model to simulate the B cell maturation process in the 10-day primary immune response. The second scale uses a delay ordinary differential equation system to model the immune responses in the 6-month lifespan of zebrafish. The generalized NK model shows that mature B cells specific to one antigen mostly possess a single VDJ recombination. The probability that mature B cells in two zebrafish have the same VDJ recombination increases with the B cell population size or the B cell selection intensity and decreases with the B cell hypermutation rate. The ODE model shows a distribution of correlation in the VDJ usage of the B cell repertoires in two six-month-old zebrafish that is highly similar to that from experiment. This work presents a simple theory to explain the experimentally observed correlation in VDJ usage of distinct zebrafish B cell repertoires after an immune response. [Preview Abstract] |
Monday, March 21, 2011 3:42PM - 3:54PM |
D39.00007: Modelling Nanoparticle Diffusion into Cancer Tumors Vishwa Priya Podduturi, Pedro Derosa Cancer is one of the major, potentially deadly diseases and has been for years. Non-specific delivery of the drug can damage healthy tissue seriously affecting in many cases the patient's living condition. Nanoparticles are being used for a targeted drug delivery thereby reducing the dose. In addition, metallic nanoparticles are being used in thermal treatment of cancer cells where nanoparticles help concentrate heat in the tumor and away from living tissue. We proposed a model that combines random walk with diffusion principles. The particle drift velocity is taken from the Hagen-Poiseuille equation and the velocity profile of the particle at the pores in the capillary wall is obtained using the Coventorware software. Pressure gradient and concentration gradient through the capillary wall are considered. Simulations are performed in Matlab using the Monte Carlo technique. Number of particles leaving the blood vessel through a pore is obtained as a function of blood pressure, the osmotic pressure, temperature, particle concentration, blood vessel radius, and pore size, and the relative effect of each of the parameters is discussed. [Preview Abstract] |
Monday, March 21, 2011 3:54PM - 4:06PM |
D39.00008: ABSTRACT WITHDRAWN |
Monday, March 21, 2011 4:06PM - 4:18PM |
D39.00009: Hearing and Infinite-Period Bifurcations Seung Ji, Dolores Bozovic, Robijn Bruinsma Auditory and vestibular systems present us with biological sensors that can achieve sub-nanometer sensitivity orders of magnitude in the dynamic range, while operating in a fluid-immersed, room-temperature environment. While the mechanisms behind this extreme sensitivity and robustness of the inner ear have not been fully explained, nonlinear response has been shown to be crucial to its proper function. Recent experiments have recorded innate motility of hair cells of the bullfrog sacculus, under varying degrees of steady-state offset. The bundle deflection was shown to suppress or enhance spontaneous oscillations, and affect the sensitivity of the mechanical response. We will present a theoretical model based on cubic nonlinearity and show that in different parameter regimes, the system can be induced to cross a supercritical Hopf bifurcation, an infinite-period bifurcation, or a multi-critical point. Comparing the numerical simulation to the experiment, we will present evidence that the multi-critical point corresponds most closely to the dynamic state of saccular hair cells. Further, we will discuss the crossing of the bifurcation, and the sensitivity of the phase-locked response in various frequency regimes. [Preview Abstract] |
Monday, March 21, 2011 4:18PM - 4:30PM |
D39.00010: Axonal Transport and Morphogenesis near Retinal Excavation of the eye Yinyun Li, Anthony Brown, Peter Jung Neurofilaments(NFs) represent the main space-filling elements of mature axons. NFs are transported on microtubule (MT) tracks along the axon at a slow rate of $mm/day$ and thus form a dynamic cytoskeleton. During development, the optic nerve forms a sharp increase of caliber at about $150 \mu m$ from the retinal excavation of the eye. Our key hypothesis is a relation between NF kinetics and nerve morphology based on the continuity of the active flow of NFs. We use computational modeling of axonal transport to infer modulation of NF kinetics consistent with the observed increase of nerve caliber. We show that the inferred kinetics is also consistent with reported spatial distribution of NFs and MTs near the retinal excavation. We further show that the predicted time course of development of the observed nerve swelling is consistent with the time course of animal development. [Preview Abstract] |
Monday, March 21, 2011 4:30PM - 4:42PM |
D39.00011: Hydroxyapatite in Physiological Environment Alexander Slepko, Alexander A. Demkov A carbonated form of hydroxyapatite (HA) [Ca$_{10}$(PO$_{4})_{6}$(OH)$_{2}$] is one of the most abundant materials in mammal bone. It crystallizes within the spaces between tropocollagen protein chains in an aqueous solution and strengthens the bone tissue. An emerging application of synthetic HA is bone repair and replacement. Bulk electronic and chemical properties of HA were studied theoretically recently. However, the absorption of H$_{2}$O molecules and amino acids of the tropocollagen chains at HA surfaces remains an area of active research. Using density functional theory we analyze the electronic properties and surface energetics of HA for different orientations and terminations and generate a theoretical surface phase diagram of HA. The reactivity of these surface models is analyzed using the frontier orbital approach. We find two dominant surfaces which are most stable over the widest chemical range. However, we expect them to show little surface reactivity. Using a HA slab with a highly reactive surface we build atomistic models of HA covered with up to one monolayer of water and analyze interactions between this surface and the water molecules. [Preview Abstract] |
Monday, March 21, 2011 4:42PM - 4:54PM |
D39.00012: Excitable signal relay in Dictyostelium discoideum Troy Mestler, David Schwab, Pankaj Mehta, Thomas Gregor The social amoeba D. discoideum transitions when starved from a collection of individual cells into a multicellular spore-complex. During this process, amoebae display several interesting phenomena including intercellular signaling, pattern formation, and cell differentiation. At the heart of these phenomena is the exchange of the signaling molecule cyclic-AMP, which has previously been extensively studied using a variety of indirect methods. Here we employ a sensor that uses a compound fluorescent protein whose emission spectrum changes in the presence of bound cyclic AMP to directly monitor, in real time and in vivo, intracellular cAMP concentrations. We use cells expressing this sensor in microchemostats to study intracellular cAMP concentrations at the single-cell level in response to precise, dynamically-controlled external cAMP stimulation. Specifically, we show that these cells display excitability much like that found in neurons and agree experimentally quite well with a modified FitzHugh-Nagumo dynamical systems model. This single-cell model sets groundwork for a comprehensive multicellular model that promises to explain emergent behavior in D. discoideum. [Preview Abstract] |
Monday, March 21, 2011 4:54PM - 5:06PM |
D39.00013: Modeling Intracellular Oscillations and Polarity Transition in Fission Yeast Tyler Drake, Maitreyi Das, Fulvia Verde, Dimitrios Vavylonis Fission yeast, a pill-shaped model organism, restricts growth to its tips. These cells maintain an asymmetric growth state, growing at only one tip, until they meet length and cell-cycle requirements. With these met, they grow at both. The mechanism of this transition, new-end take-off (NETO), remains unclear. We find that NETO occurs due to long-range competition for fast-diffusing signaling protein Cdc42 between the old and new tips. From experimental results, we suppose that symmetric tips compete for Cdc42, which triggers growth. We describe a symmetric growth model based on competition between tips. This model restricts short cells to monopolar states while allowing longer cells to be bipolar. Autocatalytic Cdc42 recruiting at both cells tips leads to broken symmetry, and the recruiting cuts off as tip Cdc42 levels saturate. Non-linear differential equations describe the model, with stable attractors indicating valid distributions. Linear stability analysis and numerical methods identify stable fixed points over a twofold increase in cell length. The model reproduces qualitative behavior of the organism. We show that observed pole-to-pole Cdc42 oscillations may facilitate the polarity transition and discuss their relationship to the Min system in E. Coli. [Preview Abstract] |
Monday, March 21, 2011 5:06PM - 5:18PM |
D39.00014: Biomineral Structure and Strength of Barnacle Exoskeletons Nathan Swift Studying the construction of organic-inorganic compound structures through biomineralization is potentially very useful. During biomineral formation, organisms restructure naturally occurring minerals in conjunction with their own organically produced minerals to create new structures. While there is extensive knowledge about material properties and structure of the raw minerals themselves, insight into how specific biomineral structures and compounds contribute to an object's mechanical properties is lacking. In this study, the exoskeletons of barnacles from the genus \textit{Balanus} were examined, both for their physical structure (how they're put together) and for their mechanical properties (strength, hardness, and elasticity). Scanning electron microscopy produced close-up, detailed images of the inner shell structure to determine what type of structure barnacles build during exoskeleton formation. Energy dispersive x-ray spectroscopy was used to map the elemental components of the shells. Nanoindentation tested the mechanical properties of these mapped structures to determine how certain characteristics of the exoskeleton contribute to its mechanical properties. [Preview Abstract] |
Monday, March 21, 2011 5:18PM - 5:30PM |
D39.00015: Enhancing mechanical properties of calcite by Mg substitutions: An ab initio study Pavlina Elstnerova, Martin Friak, Tilmann Hickel, Helge Otto Fabritius, Liverios Lymperakis, Michal Petrov, Dierk Raabe, Joerg Neugebauer, Svetoslav Nikolov, Andreas Zigler, Sabine Hild Arthropoda representing a majority of all known animal species are protected by an exoskeleton formed by their cuticle. The cuticle represents a hierarchically structured multifunctional bio-composite based on chitin and proteins. Some groups like Crustacea reinforce the load-bearing parts of their cuticle with calcite. As the calcite sometimes contains Mg it was speculated that Mg may have a stiffening impact on the mechanical properties of the cuticle. We present a theoretical parameter-free quantum-mechanical study of thermodynamic, structural and elastic properties of Mg-substituted calcite. Our results show that substituting Ca by Mg causes an almost linear decrease in the crystal volume with Mg concentration and of substituted crystals. As a consequence the calcite crystals become stiffer giving rise e.g. to substantially increased bulk moduli. [Preview Abstract] |
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