The Cell Penetrating Peptides pVEC and W2-pVEC Induce Transformation of Gel Phase Domains in Phospholipid Bilayers without Affecting Their Integrity

The cell penetrating peptide (CPP) pVEC has been shown to translocate efficiently the plasma membrane of different mammalian cell lines by a receptor-independent mechanism without exhibiting cellular toxicity. This ability renders CPPs of broad interest in cell biology, biotechnology, and drug deliv...

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Veröffentlicht in:Biochemistry (Easton) 2006-03, Vol.45 (11), p.3598-3609
Hauptverfasser: Herbig, Michael E, Assi, Fabiano, Textor, Marcus, Merkle, Hans P
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Sprache:eng
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Zusammenfassung:The cell penetrating peptide (CPP) pVEC has been shown to translocate efficiently the plasma membrane of different mammalian cell lines by a receptor-independent mechanism without exhibiting cellular toxicity. This ability renders CPPs of broad interest in cell biology, biotechnology, and drug delivery. To gain insight into the interaction of CPPs with biomembranes, we studied the interaction of pVEC and W2-pVEC, an Ile → Trp modification of the former, with phase-separated supported phospholipid bilayers (SPB) by atomic force microscopy (AFM). W2-pVEC induced a transformation of dipalmitoyl phosphatidylcholine (DPPC) domains from a gel phase state via an intermediate state with branched structures into essentially flat bilayers. With pVEC the transformation followed a similar pathway but was slower. Employing fluorescence polarization, we revealed the capability of the investigated peptides to increase the fluidity of DPPC domains as the underlying mechanism of transformation. Due to their tighter packing, sphingomyelin (SM) domains were not transformed. By combination, AFM observations, dynamic light scattering studies, and liposome leakage experiments indicated that bilayer integrity was not compromised by the peptides. Transformation of gel phase domains in SPB by CPPs represents a novel aspect in the discussion on uptake mechanisms of CPPs.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi050923c