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Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.


ABSTRACT: 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.

SUBMITTER: Allolio C 

PROVIDER: S-EPMC6255155 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.

Allolio Christoph C   Magarkar Aniket A   Jurkiewicz Piotr P   Baxová Katarína K   Javanainen Matti M   Mason Philip E PE   Šachl Radek R   Cebecauer Marek M   Hof Martin M   Horinek Dominik D   Heinz Veronika V   Rachel Reinhard R   Ziegler Christine M CM   Schröfel Adam A   Jungwirth Pavel P  

Proceedings of the National Academy of Sciences of the United States of America 20181105 47


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 rea  ...[more]

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