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
- is 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 newly
identified passive cell penetration mechanism bears analogy to vesicle
fusion induced by calcium ions, indicating