Toward a Discrete Molecular Dynamics Coarse-Grained Lipid Bilayer Model for Studies of amyloid beta -Membrane Interactions

POSTER

Abstract

Despite being the focus of intense study, the exact mechanism underlying Alzheimer’s disease is not well understood. Soluble, low molecular weight assemblies formed by amyloid beta-protein (Abeta), called oligomers, are hypothesized to trigger the Alzheimer’s disease pathology by causing synaptic failure that involves interactions between Abeta and the membrane. Several studies using a computational method called discrete molecular dynamics (DMD) combined with a coarse-grained protein model have demonstrated that many aspects of Abeta oligomer formation and structure can be captured and predicted by this efficient approach. Here, we aim to expand this DMD approach to include a model of a lipid bilayer to be combined with the protein model in an effort to examine Abeta -membrane interactions. We have developed a course-grained lipid model which can self-assemble into a membrane-like structure. Next, this lipid bilayer model will be characterized and the parameters of the model adjusted to achieve the correct cross-layer density and diffusion constant, and to capture multiple phases transitions observed in real membranes. Finally, we will investigate interactions of a lipid bilayer with Abeta oligomers which are expected to disrupt the lipid bilayer. This research will provide insights into the possible mechanisms underlying Abeta oligomer-mediated cytotoxicity.

Authors

  • Blake Antos

    Drexel University

  • Debbie Andres

    Department of Applied Physics and Department of Physics, Columbia University, Istituto Italiano di Tecnologia, Graphene Labs, Italy, Department of Physics and Astronomy, Purdue University, Department of Electrical Engineering, Princeton University, Department of Applied Physics and Applied Mathematics, Columbia University, NJIT, New Jersey Inst of Technology, New Jersey Inst of Tech, New Jersey Institute of Technology, Center for Advanced Radiation Sources, University of Chicago, High Pressure Science and Technology Advanced Research, State University of New York at Stony Brook, Rutgers University, NIST, Brookhaven National Laboratory, University of Chicago, University of South Florida, ETH Zurich, Max Planck POSTECH/Korea Research Initiative, University of Virginia, Rutgers University - Camden, New Jersey Institute of technology, Shaanxi Normal University, Pohang Science and Technology University, Sungkyunkwan University, Northern Illinois University and Argonne National Laboratory, Beijing National Laboratory for Condensed Matter Physics , and Institute of Physics, Chinese Academy of Sciences, Rutgers U., Orsova Engineers, U.S. Naval Research Laboratory, Center for Space Science and Engineering Research, Virginia Tech, Virginia., Princeton University, NASA Goddard Space Flight Center, Villanova University, SOFIA/USRA, Jet Propulsion Laboratory, Hudson Regional Health Commision, Rutgers University, College of William & Mary, Department of Physics, Drexel University, Drexel University, Drexel Universty, University of Massachusetts Amherst, Pohang Institue of Science and Technology, Indiana University - Purdue University Indianapolis, Department of Physics, University of Maryland, Naval Research Laboratory, Towson Univ, Rice University, Independence Blue Cross Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, Department of Physics, Temple University, PulseTorr LLC, Department of Chemistry, West Chester University, Department of Physics, West Chester University, College of William and Mary Dept. of Physics, University of Virginia Dept. of Materials Science and Engineering, United States Naval Academy, Rutgers The State University of New Jersey, Univ of Maryland-College Park, Los Alamos National Laboratory, POSTECH, New Jersey Institute of Technology, Department of Electrical and Computer Engineering, HamSCI/ARRL, Virginia Tech, Rutgers University-Camden, University of Washington, Rutgers, The State University of New Jersey