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

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Allolio , C , Magarkar , A , Jurkiewicz , P , Baxova , K , Javanainen , M , Mason , P E , Sachl , R , Cebecauer , M , Hof , M , Horinek , D , Heinz , V , Rachel , R , Ziegler , C M , Schröfel , A & Jungwirth , P 2018 , ' 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 , vol. 115 , no. 47 , pp. 11923-11928 . https://doi.org/10.1073/pnas.1811520115

Title: Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore
Author: Allolio, Christoph; Magarkar, Aniket; Jurkiewicz, Piotr; Baxova, Katarina; Javanainen, Matti; Mason, Philip E.; Sachl, Radek; Cebecauer, Marek; Hof, Martin; Horinek, Dominik; Heinz, Veronika; Rachel, Reinhard; Ziegler, Christine M.; Schröfel, Adam; Jungwirth, Pavel
Contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Czech Academy of Sciences
Date: 2018-11-20
Language: eng
Number of pages: 6
Belongs to series: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
URI: http://hdl.handle.net/10138/272999
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.
Subject: cell-penetrating peptide
membrane fusion
fluorescence microscopy
electron microscopy
molecular dynamics
PHOSPHOLIPID-VESICLES
PLASMA-MEMBRANE
CURVATURE
MECHANISM
TRANSLOCATION
MODEL
CA2+
INTERNALIZATION
SIMULATIONS
LIPOSOMES
1182 Biochemistry, cell and molecular biology
216 Materials engineering
317 Pharmacy
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