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

Allolio, Christoph and Magarkar, Aniket and Jurkiewicz, Piotr and Baxova, Katarina and Javanainen, Matti and Mason, Philip E. and Sachl, Radek and Cebecauer, Marek and Hof, Martin and Horinek, Dominik and Heinz, Veronika and Rachel, Reinhard and Ziegler, Christine M. and Schrofel, Adam and Jungwirth, Pavel (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, 115 (47). pp. 11923-11928. ISSN 0027-8424,

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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.

Item Type: Article
Uncontrolled Keywords: PHOSPHOLIPID-VESICLES; PLASMA-MEMBRANE; CURVATURE; MECHANISM; TRANSLOCATION; MODEL; CA2+; INTERNALIZATION; SIMULATIONS; LIPOSOMES; cell-penetrating peptide; membrane fusion; fluorescence microscopy; electron microscopy; molecular dynamics
Subjects: 500 Science > 540 Chemistry & allied sciences
500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Christine Ziegler
Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie > Chair of Chemistry VI - Physical Chemistry (Solution Chemistry) > Prof. Dr. Dominik Horinek
Depositing User: Dr. Gernot Deinzer
Date Deposited: 09 Oct 2019 06:31
Last Modified: 09 Oct 2019 06:31
URI: https://pred.uni-regensburg.de/id/eprint/13529

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