This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.105.061697v1 89/6/4300    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Plénat, T. Articles by Le Grimellec, C. Search for Related Content PubMed PubMed Citation Articles by Plénat, T. Articles by Le Grimellec, C.

Coexistence of a Two-States Organization for a Cell-Penetrating Peptide in Lipid Bilayer

Nanostructures et Complexes Membranaires, Centre de Biochimie Structurale, INSERM UMR 554, CNRS UMR 5048-Université Montpellier I, 34090 Montpellier Cedex, France

Correspondence: Address reprint requests to Christian Le Grimellec, Nanostructures et Complexes Membranaires, CBS, INSERM UMR 554, 29 rue de Navacelles, 34090 Montpellier Cedex, France. Tel.: 33-467-41-79-07; Fax: 33-467-41-79-13; E-mail: clg{at}cbs.cnrs.fr.

Primary amphipathic cell-penetrating peptides transport cargoes across cell membranes with high efficiency and low lytic activity. These primary amphipathic peptides were previously shown to form aggregates or supramolecular structures in mixed lipid-peptide monolayers, but their behavior in lipid bilayers remains to be characterized. Using atomic force microscopy, we have examined the interactions of P₍₎, a primary amphipathic cell-penetrating peptide which remains -helical whatever the environment, with dipalmitoylphosphatidylcholine (DPPC) bilayers. Addition of P₍₎ at concentrations up to 5 mol % markedly modified the supported bilayers topography. Long and thin filaments lying flat at the membrane surface coexisted with deeply embedded peptides which induced a local thinning of the bilayer. On the other hand, addition of P₍₎ only exerted very limited effects on the corresponding liposome's bilayer physical state, as estimated from differential scanning calorimetry and diphenylhexatriene fluorescence anisotropy experiments. The use of a gel-fluid phase separated supported bilayers made of a dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine mixture confirmed both the existence of long filaments, which at low peptide concentration were preferentially localized in the fluid phase domains and the membrane disorganizing effects of 5 mol % P₍₎. The simultaneous two-states organization of P₍₎, at the membrane surface and deeply embedded in the bilayer, may be involved in the transmembrane carrier function of this primary amphipathic peptide.

This article has been cited by other articles:

				T. A. Spurlin and A. A. Gewirth Poly-L-Lysine-Induced Morphology Changes in Mixed Anionic/Zwitterionic and Neat Zwitterionic-Supported Phospholipid Bilayers Biophys. J., October 15, 2006; 91(8): 2919 - 2927. [Abstract] [Full Text] [PDF]