title: Phospholipid flip-flop modulated by transmembrane peptides WALP and melittin.
abstract: Select transmembrane proteins found in biogenic membranes are known to facilitate rapid bidirectional flip-flop of lipids between the membrane leaflets, while others have no little or no effect. The particular characteristics which determine the extent to which a protein will facilitate flip-flop are still unknown. To determine if the relative polarity of the transmembrane protein segment influences its capacity for facilitation of flip-flop, we have studied lipid flip-flop dynamics for bilayers containing the peptides WALP(23) and melittin. WALP(23) is used as a model hydrophobic peptide, while melittin consists of both hydrophobic and hydrophilic residues. Sum-frequency vibrational spectroscopy (SFVS) was used to characterize the bilayers and determine the kinetics of flip-flop for the lipid component, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), within the mixed bilayers. The kinetic data were utilized to determine the activation thermodynamics for DSPC flip-flop in the presence of the peptides. Melittin was found to significantly reduce the free energy barrier to DSPC flip-flop when incorporated into the bilayer at 1mol.%, while incorporation of WALP(23) at the same concentration led to a more modest reduction of the free energy barrier. The possible mechanisms by which these peptides facilitate flip-flop are analyzed and discussed in terms of the observed activation thermodynamics.
authors.affiliation: University of Utah Department of Chemistry, Salt Lake City, 84112, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Anglin
authors.forename: Krystal L
authors.initials: KL
authors.lastname: Brown
authors.forename: John C
authors.initials: JC
authors.lastname: Conboy
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry; D008555:Melitten / Q000737:chemistry*; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; D010743:Phospholipids; D008555:Melitten