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

0498461 - ÚOCHB 2019 RIV US eng J - Journal Article
Allolio, Christoph - Magarkar, Aniket - Jurkiewicz, Piotr - Baxová, Katarína - Javanainen, Matti - Mason, Philip E. - Šachl, Radek - Cebecauer, Marek - Hof, Martin - Horinek, D. - Heinz, V. - Rachel, R. - Ziegler, C. M. - Schröfel, A. - Jungwirth, Pavel
Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 115, č. 47 (2018), s. 11923-11928. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA ČR(CZ) GA16-01074S; GA ČR GA17-03160S
Institutional support: RVO:61388963 ; RVO:61388955
Keywords : cell-penetrating peptide * membrane fusion * fluorescence microscopy * electron microscopy * molecular dynamics
OECD category: Physical chemistry; Physical chemistry (UFCH-W)
Impact factor: 9.580, year: 2018
https://www.pnas.org/content/115/47/11923

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.
Permanent Link: http://hdl.handle.net/11104/0290827