title: On the microscopic and mesoscopic perturbations of lipid bilayers upon interaction with the MPER domain of the HIV glycoprotein gp41.
abstract: The effect of the 665-683 fragment of the HIV fusion glycoprotein 41, corresponding to the MPER domain of the protein and named gp41MPER, on the microscopic structure and mesoscopic arrangement of palmitoyl oleoyl phosphatidylcholine (POPC) and POPC/sphingomyelin (SM)/cholesterol (CHOL) lipid bilayers is analyzed. The microscopic structuring of the bilayers has been studied by Electron Spin Resonance (ESR) spectroscopy, using glycerophosphocholines spin-labelled in different positions along the acyl chain. Transitions of the bilayer liquid crystalline state have been also monitored by Differential Scanning Calorimetry (DSC). Changes of the bilayers morphology have been studied by determining the dimension of the liposomes through Dynamic Light Scattering (DLS) measurements. The results converge in showing that the sample preparation procedure, the bilayer composition and the peptide/lipid ratio critically tune the lipid response to the peptide/membrane interaction. When gp41MPER is added to preformed liposomes, it positions at the bilayer interface and the lipid perturbation is limited to the more external segments. In contrast, if the peptide is mixed with the lipids during the liposome preparation, it assumes a trans-membrane topology. This happens at all peptide/lipid ratios for fluid POPC bilayers, while in the case of rigid POPC/SM/CHOL membranes a minimum ratio has to be reached, thus suggesting peptide self-aggregation to occur. Peptide insertion results in a dramatic increase of the lipid ordering and bilayer stiffening, which reflect in significant changes in liposome average dimension and distribution. The biological implications of these findings are discussed.
authors.affiliation: Department of Chemical Science - University of Naples "Federico II", Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Oliva
authors.affiliation: Department of Chemical Science - University of Naples "Federico II", Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Emendato
authors.affiliation: Department of Chemical, Materials and Production Engineering - University of Naples "Federico II", Piazzale Tecchio 80, 80125 Naples, Italy; CSGI, Consorzio interuniversitario per lo sviluppo dei Sistemi a Grande Interfase, via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vitiello
authors.affiliation: Department of Chemical Science - University of Naples "Federico II", Monte Sant'Angelo, 80126 Naples, Italy; CSGI, Consorzio interuniversitario per lo sviluppo dei Sistemi a Grande Interfase, via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy.
authors.forename: Augusta
authors.initials: A
authors.lastname: De Santis
authors.affiliation: Department of Pharmaceutical Science - University of Salerno, via Ponte Don Melillo, 84084 Fisciano, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Grimaldi
authors.affiliation: Department of Pharmaceutical Science - University of Salerno, via Ponte Don Melillo, 84084 Fisciano, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
authors.affiliation: CSGI, Consorzio interuniversitario per lo sviluppo dei Sistemi a Grande Interfase, via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy; Department of Biotechnology, Chemistry and Pharmacy - University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Busi
authors.affiliation: Department of Chemical Science - University of Naples "Federico II", Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Pompea
authors.initials: P
authors.lastname: Del Vecchio
authors.affiliation: Department of Chemical Science - University of Naples "Federico II", Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Petraccone
authors.affiliation: Department of Chemical Science - University of Naples "Federico II", Monte Sant'Angelo, 80126 Naples, Italy; CSGI, Consorzio interuniversitario per lo sviluppo dei Sistemi a Grande Interfase, via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy. Electronic address: gerardino.derrico@unina.it.
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
mesh_terms: D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000737:chemistry; D000067493:Dynamic Light Scattering; D004578:Electron Spin Resonance Spectroscopy; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D050866:Liquid Crystals; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D010446:Peptide Fragments; D010713:Phosphatidylcholines / Q000737:chemistry; D000072417:Protein Domains; D013109:Sphingomyelins / Q000737:chemistry
chemical_list: D015700:HIV Envelope Protein gp41; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D008565:Membrane Proteins; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D013109:Sphingomyelins; C000624239:gp41 (665-683), HIV; C514787:gp41 protein, Human immunodeficiency virus 1; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: Bilayer structure; Differential scanning calorimetry; Electron spin resonance; Fusion glycoprotein; HIV; Lipid ordering