Non-Metabolic Membrane Tubulation and Permeability Induced by Bioactive Peptides 英文参考文献.docVIP

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Non-Metabolic Membrane Tubulation and Permeability Induced by Bioactive Peptides 英文参考文献.doc

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Non-Metabolic Membrane Tubulation and Permeability Induced by Bioactive Peptides 英文参考文献

Non-MetabolicMembraneTubulationandPermeability InducedbyBioactivePeptides AntoninLamazie`re1,2,FabienneBurlina3,ClaudeWolf1,2,Ge′rardChassaing3,GermainTrugnan1,2,JesusAyala-Sanmartin1,2 * 1InstitutNationaldelaSante′ etdelaRechercheMe′dicale(INSERM),UMR538,CHUSaintAntoine,Paris,France,2Universite′ PierreetMarieCurie, CHUSaintAntoine,Paris,France,3UMRCentreNationaldelaRechercheScientifique(CNRS)7613,Universite′ PierreetMarieCurie,Paris,France Background.Basiccell-penetratingpeptidesarepotentialvectorsfortherapeuticmoleculesanddisplayantimicrobialactivity. Thepeptide-membranecontactisthefirststepofthesequentialprocessesleadingtopeptideinternalizationandcellactivity. However,themolecularmechanismsinvolvedinpeptide-membraneinteractionarenotwellunderstoodandarefrequently controversial. Herein, we compared the membrane activities of six basic peptides with different size, charge density and amphipaticity: Two cell-penetrating peptides (penetratin and R9), three amphipathic peptides and the neuromodulator substance P. Methodology/Principal Findings. Experiments of X ray diffraction, video-microscopy of giant vesicles, fluorescence spectroscopy, turbidimetry and calcein leakage from large vesicles are reported. Permeability and toxicity experimentswereperformedonculturedcells.Thepeptidesshoweddifferences inbilayerthicknessperturbations,vesicles aggregationandlocalbendingpropertieswhichformlipidictubularstructures.Thesestructuresinvadethevesiclelumenin the absence of exogenous energy. Conclusions/Significance. We showed that the degree of membrane permeabilization withamphipathicpeptidesisdependentonbothpeptidesizeandhydrophobicnatureoftheresidues.Weproposeamodelfor peptide-induced membrane perturbations that explains the differences in peptide membrane activities and suggests the existenceofafacilitated‘‘physicalendocytosis,’’whichrepresentsanewpathwayforpeptidecellularinternalization. Citation: Lamazie`re A,BurlinaF,WolfC,ChassaingG,TrugnanG, etal