Lipid domain separation, bilayer thickening and pearling induced by the cell penetrating peptide penetratin

• Published in: Biochimica et biophysica acta 2010-12, Vol.1798 (12), p.2223-2230
• Main Authors: Lamazière, Antonin, Maniti, Ofelia, Wolf, Claude, Lambert, Olivier, Chassaing, Gérard, Trugnan, Germain, Ayala-Sanmartin, Jesus
• Format: Article
• Language: English
• Subjects: Biochemistry; Biochemistry, Molecular Biology; Biophysics; Carrier Proteins - chemistry; Cell-Penetrating Peptides - chemistry; Chemical Sciences; Life Sciences; Lipid Bilayers - chemistry; Lipid phase separation; Membrane curvature; Membrane Lipids - chemistry; Membrane pearling; Membrane thickening; Organic chemistry; Penetratin; Physical endocytosis; Structural Biology
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2009.12.024

Protein membrane transduction domains are able to translocate through cell membranes. This capacity resulted in new concepts on cell communication and in the design of vectors for internalization of active molecules into cells. Penetratin crosses the plasma membrane by a receptor and metabolic energy-independent mechanism which is at present unknown. A better knowledge of its interaction with phospholipids will help to understand the molecular mechanisms of cell penetration. Here, we investigated the role of lipid composition on penetratin induced membrane perturbations by X-ray diffraction, microscopy and 31P-NMR. Penetratin showed the ability to induce phospholipid domain separation, membrane bilayer thickening, formation of vesicles, membrane undulations and tubular pearling. These data demonstrate its capacity to increase membrane curvature and suggest that dynamic phospholipid–penetratin complexes can be organized in different structural arrangements. These properties and their implications in peptide membrane translocation capacity are discussed.