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Binding of amyloid peptides to lipid bilayers: effects of ions and lipid content

ORAL

Abstract

In amyloid diseases, cell toxicity can emerge from interactions of peptides with the cell membrane. In particular, amyloid peptides can form pores in the cell membrane and/or induce lipid loss through a detergent-like mechanism. Several factors have been shown to modulate the magnitude of these peptides-bilayer interactions, which can enhance or inhibit cell toxicity. These factors include lipid composition and the presence of ions in the solution. Here, we perform all-atom molecular dynamics simulations to provide an understanding at the atomic level of peptide-bilayer interactions and their modulation by Ca and selected lipids. Simulations are performed using amphipathic sequences inspired by amyloid peptides and bilayers make from palmitoyloleoyl-phosphatidycholine lipids. We find that both electrostatic and hydrophobic interactions contribute to peptide-bilayer binding. Specifically, binding is initiated with positively charged residues interacting with lipid head groups. Hydrophobic interactions sustain this bound state. The latter accounts for an irreversible bound state at room temperature. I will discuss these mechanisms in detail as well as how they are affected by Ca and selected lipid content of the bilayer.

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Authors

  • Yanxing Yang

    New Jersey Inst of Tech, Department of Physics, New Jersey Institute of Tech

  • Anuradha Gupta

    New Jersey Inst of Tech, Pennsylvania State University, Bard College, University of Mississippi, Drexel Univ, Collaborator, University of Dayton, Morgan State University, Louisiana State University, University of Geneva, Instituto Superior Tecnico - Lisboa, Department of Biochemistry and Molecular Biology, Rutgers University, Institute for Quantitative Biomedicine, Rutgers University, Pennsylvania State University, and University of Illinois at Urbana-Champaign, University of Illinois at Urbana-Champaign, Department of Chemical Engineering, New Jersey Institute of Technology, Department of Physics and Astronomy, Rutgers University-New Brunswick, Department of Physics, Rutgers University, Max-Planck-Institut für Festkörperforschung, Heisenbergstrasse 1, 70569 Stuttgart, Germany, Department of Physics and Fribourg Center for Nanomaterials, University of Fribourg, Chemin du Musée 3, CH-1700 Fribourg, Switzerland, The MacDiarmid Institute for Advanced Materials and Nanotechnology, 1010 Auckland, New Zealand, Department of Physics, College of William & Mary, Williamsburg, VA 23187-8795, USA, New Jersey Institute of Technology, Newark, NJ, USA, University of California, Los Angeles, CA, USA, University of California, Berkeley, CA, USA, Space Research Institute of RAS, Moscow, Russia, Georgetown University, Institut Polytechnique de Paris, University of Delaware, Brookhaven National Laboratory, San Diego State University, University of Chicago, University of Illinois at Chicago, Argonne National Laboratory, Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854, USA, University of Washington

  • Anuradha Gupta

    New Jersey Inst of Tech, Pennsylvania State University, Bard College, University of Mississippi, Drexel Univ, Collaborator, University of Dayton, Morgan State University, Louisiana State University, University of Geneva, Instituto Superior Tecnico - Lisboa, Department of Biochemistry and Molecular Biology, Rutgers University, Institute for Quantitative Biomedicine, Rutgers University, Pennsylvania State University, and University of Illinois at Urbana-Champaign, University of Illinois at Urbana-Champaign, Department of Chemical Engineering, New Jersey Institute of Technology, Department of Physics and Astronomy, Rutgers University-New Brunswick, Department of Physics, Rutgers University, Max-Planck-Institut für Festkörperforschung, Heisenbergstrasse 1, 70569 Stuttgart, Germany, Department of Physics and Fribourg Center for Nanomaterials, University of Fribourg, Chemin du Musée 3, CH-1700 Fribourg, Switzerland, The MacDiarmid Institute for Advanced Materials and Nanotechnology, 1010 Auckland, New Zealand, Department of Physics, College of William & Mary, Williamsburg, VA 23187-8795, USA, New Jersey Institute of Technology, Newark, NJ, USA, University of California, Los Angeles, CA, USA, University of California, Berkeley, CA, USA, Space Research Institute of RAS, Moscow, Russia, Georgetown University, Institut Polytechnique de Paris, University of Delaware, Brookhaven National Laboratory, San Diego State University, University of Chicago, University of Illinois at Chicago, Argonne National Laboratory, Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854, USA, University of Washington