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Cell Penetration and Membrane Fusion: Two Sides of the Same Coin

Cell Penetration and Membrane Fusion: Two Sides of the Same Coin

Datum: 22. Juni 2017 10:30

Ort: Allmandring 3, Seminarraum 1.079

Veranstalter: ICP

Cell Penetration and Membrane Fusion: Two Sides of the Same Coin

Pavel Jungwirth, Czech Academy of Sciences, Prag

Cell penetrating peptides have a unique potential for targeted drug delivery, therefore, mechanistic understanding of their membrane action has been sought since their discovery over 20 years ago. While ATP-driven endocytosis is known to play a major role in their internalization, there has been also ample evidence for the importance of passive translocation for which the direct mechanism, where the peptide is thought to directly pass through the membrane via a temporary pore, has been widely advocated. In this talk, I will question this view and demonstrate that arginine-rich cell penetrating peptides instead enter vesicles by inducing multilamellarity and fusion, analogously to the action of calcium ions. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. In addition, the kinetics of vesicle agglomeration and fusion by nonaarginine, nonalysine, and calcium ions are documented in real time by fluorescence techniques and the induction of multilamellar phases is revealed both via electron microscopy and fluorescence spectroscopy. We thus show that the newly identified passive cell penetration mechanism is analoguous to vesicle fusion induced by calcium ions, demonstrating that the two processes are of a common mechanistic origin.

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