Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cell-penetrating peptide-nonaarginine-are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies. This concert of experiments and simulations reveals that the identified passive cell penetration mechanism bears analogy to vesicle fusion induced by calcium ions, indicating that the two processes may share a common mechanistic origin.
- MeSH
- arginin metabolismus fyziologie MeSH
- biologický transport MeSH
- buněčná membrána metabolismus MeSH
- fúze membrán účinky léků fyziologie MeSH
- kinetika MeSH
- lipidové dvojvrstvy chemie MeSH
- membrány metabolismus MeSH
- penetrační peptidy chemie metabolismus MeSH
- peptidy chemie fyziologie MeSH
- pseudopodia metabolismus fyziologie MeSH
- simulace molekulární dynamiky MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
