title: Perturbation of a lipid membrane by amphipathic peptides and its role in pore formation.
abstract: We study the structural and energetic consequences of (alpha-helical) amphipathic peptide adsorption onto a lipid membrane and the subsequent formation of a transmembrane peptide pore. Initially, each peptide binds to the membrane surface, with the hydrophobic face of its cylinder-like body inserted into the hydrocarbon core. Pore formation results from subsequent peptide crowding, oligomerization, and eventually reorientation along the membrane normal. We have theoretically analyzed three peptide-membrane association states: interfacially-adsorbed monomeric and dimeric peptides, and the multi-peptide transmembrane pore state. Our molecular-level model for the lipid bilayer is based on a combination of detailed chain packing theory and a phenomenological description of the headgroup region. We show that the membrane perturbation free energy depends critically on peptide orientation: in the transmembrane pore state the lipid perturbation energy, per peptide, is smaller than in the adsorbed state. This suggests that the gain in conformational freedom of the lipid chains is a central driving force for pore formation. We also find a weak, lipid-mediated, gain in membrane perturbation free energy upon dimerization of interfacially-adsorbed peptides. Although the results pertain mainly to weakly-charged peptides, they reveal general properties of the interaction of amphipathic peptides with lipid membranes.
authors.affiliation: Department of Physical Chemistry and the Fritz Haber Research Center, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Zemel
authors.forename: Avinoam
authors.initials: A
authors.lastname: Ben-Shaul
authors.forename: Sylvio
authors.initials: S
authors.lastname: May
mesh_terms: D003198:Computer Simulation; D019281:Dimerization; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry*; D016062:Porosity
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D010455:Peptides; D010713:Phosphatidylcholines; C002448:1,2-linoleoylphosphatidylcholine