title: Fluid and condensed ApoA-I/phospholipid monolayers provide insights into ApoA-I membrane insertion.
abstract: Apolipoprotein A-I (ApoA-I) is a protein implicated in the solubilization of lipids and cholesterol from cellular membranes. The study of ApoA-I in phospholipid (PL) monolayers brings relevant information about ApoA-I/PL interactions. We investigated the influence of PL charge and acyl chain organization on the interaction with ApoA-I using dipalmitoyl-phosphatidylcholine, dioleoyl-phosphatidylcholine and dipalmitoyl-phosphatidylglycerol monolayers coupled to ellipsometric, surface pressure, atomic force microscopy and infrared (polarization modulation infrared reflection-absorption spectroscopy) measurements. We show that monolayer compressibility is the major factor controlling protein insertion into PL monolayers and show evidence of the requirement of a minimal distance between lipid headgroups for insertion to occur, Moreover, we demonstrate that ApoA-I inserts deepest at the highest compressibility of the protein monolayer and that the presence of an anionic headgroup increases the amount of protein inserted in the PL monolayer and prevents the steric constrains imposed by the spacing of the headgroup. We also defined the geometry of protein clusters into the lipid monolayer by atomic force microscopy and show evidence of the geometry dependence upon the lipid charge and the distance between headgroups. Finally, we show that ApoA-I helices have a specific orientation when associated to form clusters and that this is influenced by the character of PL charges. Taken together, our results suggest that the interaction of ApoA-I with the cellular membrane may be driven by a mechanism that resembles that of antimicrobial peptide/lipid interaction.
authors.affiliation: Institut de Physique de Rennes, UMR-CNRS 6251 Université de Rennes 1, Campus de Beaulieu, 35042 Rennes cedex, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Chièze
authors.forename: Victor Martin
authors.initials: VM
authors.lastname: Bolanos-Garcia
authors.forename: Mathieu
authors.initials: M
authors.lastname: Pinot
authors.forename: Bernard
authors.initials: B
authors.lastname: Desbat
authors.forename: Anne
authors.initials: A
authors.lastname: Renault
authors.forename: Sylvie
authors.initials: S
authors.lastname: Beaufils
authors.forename: Véronique
authors.initials: V
authors.lastname: Vié
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D010743:Phospholipids / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013055:Spectrophotometry, Infrared
chemical_list: D016632:Apolipoprotein A-I; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010743:Phospholipids; D011994:Recombinant Proteins