title: Diffusion as a probe of the heterogeneity of antimicrobial peptide-membrane interactions.
abstract: Many antimicrobial peptides (AMPs) function by forming various oligomeric structures and/or pores upon binding to bacterial membranes. Because such peptide aggregates are capable of inducing membrane thinning and membrane permeabilization, we expected that AMP binding would also affect the diffusivity or mobility of the lipid molecules in the membrane. Herein, we show that measurements of the diffusion times of individual lipids through a confocal volume via fluorescence correlation spectroscopy (FCS) provide a sensitive means of probing the underlying AMP-membrane interactions. In particular, results obtained with two well-studied AMPs, magainin 2 and mastoparan X, and two model membranes indicate that this method is capable of revealing structural information, especially the heterogeneity of the peptide-membrane system, that is otherwise difficult to obtain using common ensemble methods. Moreover, because of the high sensitivity of FCS, this method allows examination of the effect of AMPs on the membrane structure at very low peptide/lipid ratios.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Kathryn B
authors.initials: KB
authors.lastname: Smith-Dupont
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Gai
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004058:Diffusion; D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D054806:Magainins / Q000737:chemistry / Q000378:metabolism; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism; D013050:Spectrometry, Fluorescence / Q000379:methods; D053835:Unilamellar Liposomes / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: C546608:99mTcO(MAG2-3G3-dimer); D023181:Antimicrobial Cationic Peptides; D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; D054806:Magainins; D015335:Molecular Probes; D015609:Organotechnetium Compounds; D010455:Peptides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D053835:Unilamellar Liposomes; D029867:Xenopus Proteins; D015060:1,2-Dipalmitoylphosphatidylcholine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; C071123:mastoparan X; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
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