title: Non-metabolic membrane tubulation and permeability induced by bioactive peptides.
abstract: BACKGROUND
  Basic cell-penetrating peptides are potential vectors for therapeutic molecules and display antimicrobial activity. The peptide-membrane contact is the first step of the sequential processes leading to peptide internalization and cell activity. However, the molecular mechanisms involved in peptide-membrane interaction are not well understood and are frequently controversial. Herein, we compared the membrane activities of six basic peptides with different size, charge density and amphipaticity: Two cell-penetrating peptides (penetratin and R9), three amphipathic peptides and the neuromodulator substance P.
  
  
  RESULTS
  Experiments of X ray diffraction, video-microscopy of giant vesicles, fluorescence spectroscopy, turbidimetry and calcein leakage from large vesicles are reported. Permeability and toxicity experiments were performed on cultured cells. The peptides showed differences in bilayer thickness perturbations, vesicles aggregation and local bending properties which form lipidic tubular structures. These structures invade the vesicle lumen in the absence of exogenous energy.
  
  
  CONCLUSIONS
  We showed that the degree of membrane permeabilization with amphipathic peptides is dependent on both peptide size and hydrophobic nature of the residues. We propose a model for peptide-induced membrane perturbations that explains the differences in peptide membrane activities and suggests the existence of a facilitated "physical endocytosis," which represents a new pathway for peptide cellular internalization.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 538, CHU Saint Antoine, Paris, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Lamazière
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burlina
authors.forename: Claude
authors.initials: C
authors.lastname: Wolf
authors.forename: Gérard
authors.initials: G
authors.lastname: Chassaing
authors.forename: Germain
authors.initials: G
authors.lastname: Trugnan
authors.forename: Jesus
authors.initials: J
authors.lastname: Ayala-Sanmartin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism; D016466:CHO Cells / Q000187:drug effects; D002352:Carrier Proteins / Q000494:pharmacology; D057846:Cell-Penetrating Peptides; D006224:Cricetinae; D003412:Cricetulus; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers; D008561:Membrane Fusion; D008563:Membrane Lipids; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000145:classification / Q000494:pharmacology* / Q000633:toxicity; D010539:Permeability / Q000187:drug effects*; D017433:Protein Structure, Secondary; D013373:Substance P / Q000494:pharmacology
chemical_list: D017306:Annexin A2; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010455:Peptides; D049452:Green Fluorescent Proteins; C015462:polyarginine; D013373:Substance P; C414409:penetratin