2.B.25 The Peptide-mediated Lipid Flip-Flop (PLFF) Family
Hydrophobic peptide-accelerated transleaflet lipid movement (flip-flop) is affected by peptide sequence and vesicle composition and properties (LeBarron and London 2016). Peptides with a completely hydrophobic sequence had no effect on 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 an event that may reflect a rare state of the peptide or lipid bilayer. There is no simple relationship between peptide overall hydrophobicity and flip-flop, and flip-flop is not closely linked to whether the peptides are in a transmembrane or non-transmembrane (interfacial) inserted state. Flip-flop is not associated with peptide-induced pore formation, but peptide-accelerated flip-flop is initially faster in small (highly curved) unilamellar vesicles than in large unilamellar vesicles. Peptide-accelerated flip-flop is 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 consistent with acceleration of lipid flip-flop by peptide-induced thinning of bilayer width (LeBarron and London 2016).