title: Effect of lipid composition and amino acid sequence upon transmembrane peptide-accelerated lipid transleaflet diffusion (flip-flop).
abstract: We examined how hydrophobic peptide-accelerated transleaflet lipid movement (flip-flop) was affected by peptide sequence and vesicle composition and properties. A peptide with a completely hydrophobic sequence had little if any effect upon flip-flop. While peptides with a somewhat less hydrophobic sequence accelerated flip-flop, the half-time remained slow (hours) with substantial (0.5mol%) peptide in the membranes. It appears that peptide-accelerated lipid flip-flop involves a rare event that may reflect a rare state of the peptide or lipid bilayer. There was no simple relationship between peptide overall hydrophobicity and flip-flop. In addition, flip-flop was not closely linked to whether the peptides were in a transmembrane or non-transmembrane (interfacial) inserted state. Flip-flop was also not associated with peptide-induced pore formation. We found that peptide-accelerated flip-flop is initially faster in small (highly curved) unilamellar vesicles relative to that in large unilamellar vesicles. Peptide-accelerated flip-flop was also affected by lipid composition, being slowed in vesicles with thick bilayers or those containing 30% cholesterol. Interestingly, these factors also slow spontaneous lipid flip-flop in the absence of peptide. Combined with previous studies, the results are most consistent with acceleration of lipid flip-flop by peptide-induced thinning of bilayer width.
authors.affiliation: Dept. of Biochemistry and Cell Biology, Stony Brook, NY 11794-5215, United States.
authors.forename: Jamie
authors.initials: J
authors.lastname: LeBarron
authors.affiliation: Dept. of Biochemistry and Cell Biology, Stony Brook, NY 11794-5215, United States.
authors.forename: Erwin
authors.initials: E
authors.lastname: London
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D001692:Biological Transport; D004058:Diffusion; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry*; D008956:Models, Chemical; D009997:Osmotic Pressure; D010455:Peptides / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry; D017433:Protein Structure, Secondary; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: C078632:1-acyl-2-(12-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl)phosphatidylcholine; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010455:Peptides; D010713:Phosphatidylcholines; D010743:Phospholipids; D053835:Unilamellar Liposomes; D009327:4-Chloro-7-nitrobenzofurazan
keywords: Bilayer width; Flip-flop; Lipid asymmetry; Transmembrane peptide; Transverse diffusion; Vesicles