Direct translocation of cell penetrating peptides through membranes occurs via the formation of inverted micelles

J-M. Swiecicki, A. Bartsch, J. Tailhades, M. Di Pisa, B. Heller, C. Mansuy, F. Burlina, G. Chassaing, S. Lavielle

Research output: Contribution to conferenceAbstract


Cell penetrating peptides (CPPs) are small cationic sequences, which have the unique feature to cross cell membranes and deliver a cargo into cells. Since their discovery CPPs have become one of the most popular strategy for achieving intracellular access. Nevertheless, the exact mechanism(s) by which CPPs are able to cross membranes remain(s) to be elucidated. In living cells, there is some evidence for both endocytosis and an energy-independent penetration pathway (“direct translocation”). But even the ability of CPPs to translocate across model lipid bilayers is controversial.

In the present study, we demonstrated that CPPs are capable to penetrate spontaneously and to mediate the internalization of a bioactive cargo into large unilamellar vesicles. Using this model system, we investigated the mechanism of the translocation and observed a strong correlation between phospholipid flip-flopand CPP translocation: one anionic phospholipid flips per internalized cationic residue of the CPP. This stoichiometry is in agreement only with the inverted micelle model for CPPs direct translocation.Moreover, we recently investigated the mutual adaption at the molecular level between CPPs and phospholipids in order to understand the differences in internalization rate of the different CPPs. These results suggest a general mechanism by which CPPs may enter into cells and may help to improve the design of CPPs.
Original languageEnglish
Number of pages2
Publication statusPublished - 2014
Externally publishedYes
EventEuropean Peptide Symposium - National Palace of Culture, Sophia, Bulgaria
Duration: 31 Aug 20145 Sep 2014
Conference number: 33rd


ConferenceEuropean Peptide Symposium
Abbreviated title33EPS


  • Uptake with Peptides
  • Cell Penetrating Peptides
  • Direct Translocation
  • Phospholipid Flip-Flop
  • Membrane

Cite this

Swiecicki, J-M., Bartsch, A., Tailhades, J., Di Pisa, M., Heller, B., Mansuy, C., Burlina, F., Chassaing, G., & Lavielle, S. (2014). Direct translocation of cell penetrating peptides through membranes occurs via the formation of inverted micelles. S35-S36. Abstract from European Peptide Symposium, Sophia, Bulgaria.