title: Kinetics of cryptdin-4 translocation coupled with peptide-induced vesicle leakage.
abstract: The antimicrobial peptide cryptdin-4 (Crp4), a member of the alpha-defensin family, is shown to translocate cooperatively across phospholipid bilayers. The cooperativity of the process is manifested by translocation kinetics which vary with the peptide to lipid molar ratio. A simple association model suggests dimerization. Black lipid membrane experiments reveal that Crp4 translocation does not create well-defined aqueous pores, as is often common among peptides exhibiting cooperative translocation. Still, the efflux induced by Crp4 upon its interaction with fluorophore-loaded vesicles is shown to be a direct result of the membrane perturbation resulting from the translocation process. Leakage can be predicted by relating membrane permeability to the fraction of peptide translocated. Crp4 translocation has implications for its antimicrobial activity as internalized peptide would be available to attack intracellular targets.
authors.affiliation: Department of Chemical Engineering, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Cummings
authors.forename: T Kyle
authors.initials: TK
authors.lastname: Vanderlick
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004227:Dithionite / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D015233:Models, Statistical; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011485:Protein Binding; D023084:alpha-Defensins / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D010715:Phosphatidylglycerols; D010743:Phospholipids; D023084:alpha-Defensins; C401847:cryptdin 4, mouse; D004227:Dithionite; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol