| Sprecher |
Prof. Pavel Jungwirth,
Czech Academy of Sciences
|
| Titel |
Cell Penetration and Membrane Fusion: Two Sides of the Same Coin
|
| Abstract |
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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