Cholesterol prevents interaction of the cell-penetrating peptide transportan with model lipid membranes.
Interaction of the cell-penetrating peptide (CPP) cysteine-transportan (Cys-TP) with model lipid membranes was examined by spin-label electron paramagnetic resonance (EPR). Membranes were labeled with lipophilic spin probes and the influence of Cys-TP on membrane structure was studied. The influence of Cys-TP on membrane permeability was monitored by the reduction of a liposome-trapped water-soluble spin probe. Cys-TP caused lipid ordering in membranes prepared from pure dimyristoylphosphatidylcholine (DMPC) and in DMPC membranes with moderate cholesterol concentration. In addition, Cys-TP caused a large increase in permeation of DMPC membranes. In contrast, with high cholesterol content, at which model lipid membranes are in the so-called liquid-ordered phase, no effect of Cys-TP was observed, either on the membrane structure or on the membrane permeability. The interaction between Cys-TP and the lipid membrane therefore depends on the lipid phase. This could be of great importance for understanding of the CPP-lipid interaction in laterally heterogeneous membranes, while it implies that the CPP-lipid interaction can be different at different points along the membrane.
Arsov
Zoran
Z
Laboratory of Biophysics, JoZef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia. zoran.arsov@ijs.si
Nemec
Marjana
M
Schara
Milan
M
Johansson
Henrik
H
Langel
Ulo
U
Zorko
Matjaz
M
D002784:Cholesterol / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D019004:Galanin / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008567:Membranes, Artificial; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D014862:Wasp Venoms / Q000737:chemistry*
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D011993:Recombinant Fusion Proteins; D014862:Wasp Venoms; C110068:transportan; D019004:Galanin; D002784:Cholesterol