title: Basic cell penetrating peptides induce plasma membrane positive curvature, lipid domain separation and protein redistribution.
abstract: Basic cell penetrating peptides are tools for molecular cellular internalization of nonmembrane permeable molecules. Their uptake mechanisms involve energy-dependent and energy-independent pathways such as endocytosis, direct translocation or physical endocytosis. These mechanisms are ruled by both, the peptides physicochemical properties and structure and by the membrane lipids characteristics and organization. Herein we used plasma membrane spheres and membrane models to study the membrane perturbations induced by three arginine-rich cell penetrating peptides. Nona-arginine (R9) and the amphipathic peptide RWRRWWRRW (RW9) induced positive membrane curvature in the form of buds and membrane tubes. Membranous tubes underwent rolling resulting in formation of multilamellar membrane particles at the surface of the plasma membrane spheres. The amphipathic peptides RW9 and RRWRRWWRRWWRRWRR (RW16) provoked lipid and membrane associated protein domain separation as well as changes in membrane fluidity and cholesterol redistribution. These data suggest that membrane domains separation and the formation of multilamellar membranous particles would be involved in arginine-rich cell penetrating peptides internalization.
authors.affiliation: CNRS, UMR 7203, Laboratoire de Biomolécules, Groupe N. J. Conté, Paris, France; École Normale Supérieure, Département de Chimie, 24 rue Lhomond, 75005 Paris, France; Université Pierre et Marie Curie, 4 Place Jussieu, 75252 Paris, France.
authors.forename: Ofelia
authors.initials: O
authors.lastname: Maniti
authors.affiliation: CNRS, UMR 7203, Laboratoire de Biomolécules, Groupe N. J. Conté, Paris, France; École Normale Supérieure, Département de Chimie, 24 rue Lhomond, 75005 Paris, France; Université Pierre et Marie Curie, 4 Place Jussieu, 75252 Paris, France.
authors.forename: Hong-Rong
authors.initials: HR
authors.lastname: Piao
authors.affiliation: CNRS, UMR 7203, Laboratoire de Biomolécules, Groupe N. J. Conté, Paris, France; École Normale Supérieure, Département de Chimie, 24 rue Lhomond, 75005 Paris, France; Université Pierre et Marie Curie, 4 Place Jussieu, 75252 Paris, France. Electronic address: jesus.ayala-sanmartin@upmc.fr.
authors.forename: Jesus
authors.initials: J
authors.lastname: Ayala-Sanmartin
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D008563:Membrane Lipids; D008565:Membrane Proteins
keywords: Basic peptides; Membrane curvature; Membrane domains; Membrane rolling; Plasma membrane