Gutenberg Open Science: pH-dependent behavior of ionizable cationic lipids in mRNA-carrying lipoplexes investigated by molecular dynamics simulations

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8018

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DC Field	Value	Language
dc.contributor.author	Settanni, Giovanni	-
dc.contributor.author	Brill, Wolfgang	-
dc.contributor.author	Haas, Heinrich	-
dc.contributor.author	Schmid, Friederike	-
dc.date.accessioned	2022-10-24T08:26:23Z	-
dc.date.available	2022-10-24T08:26:23Z	-
dc.date.issued	2022	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8033	-
dc.description.abstract	Lipid-based nanoparticles and lipoplexes containing ionizable lipids are among the most successful nanocarriers for mRNA-based therapies. The molecular structure of these assemblies is still not fully understood, as well as the role played by the ionizable lipids. SAXS experiments have shown that lipoplexes including the ionizable lipid 2-dioleyloxy-N,N-dimethyl-3-aminopropane (DODMA), under specific conditions, have a lamellar structure, where lipid bilayers are separated by mRNA-rich layers, with an overall spacing between 6.5 and 8.0 nm and a complex pH-dependence. Here, the structure and dynamics of these lipoplexes are investigated at varying pH and mRNA concentration using multiscale molecular dynamics simulations. It is observed that the interaction between DODMA and RNA is slightly attractive only at low pH levels, while it becomes effectively repulsive at high and intermediate pH. This results into a pH-dependent relocation of the RNA inside the multilayers, from the lipid head groups at low pH to a more uniform distribution inside the hydrophilic slabs of the multilayers at high pH. It is also observed that at high pH, DODMA lipids shift toward the hydrophobic part of the bilayer, consequently increasing their leaflet-flipping rate, a phenomenon which may ultimately affect the fusion process of the lipoplex with the endosomal membrane.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY-NC-ND	*
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject.ddc	530 Physik	de_DE
dc.subject.ddc	530 Physics	en_GB
dc.title	pH-dependent behavior of ionizable cationic lipids in mRNA-carrying lipoplexes investigated by molecular dynamics simulations	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-8018	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 08 Physik, Mathematik u. Informatik	de
jgu.organisation.number	7940	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Macromolecular rapid communications	de
jgu.journal.volume	43	de
jgu.journal.issue	12	de
jgu.pages.alternative	2100683	de
jgu.publisher.year	2022	-
jgu.publisher.name	Wiley-VCH	de
jgu.publisher.place	Weinheim	de
jgu.publisher.issn	1521-3927	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	530	de
jgu.publisher.doi	10.1002/marc.202100683	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	JGU-Publikationen

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