SKM 2023 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 26: Focus Session mRNA Physics
BP 26.7: Vortrag
Donnerstag, 30. März 2023, 17:00–17:15, TOE 317
pH-dependent behavior of ionizable cationic lipids in mRNA-carrying lipoplexes investigated by molecular dynamics simulations — •Giovanni Settanni1,2, Wolfgang Brill3, Heinirich Haas3, and Friederike Schmid1 — 1Department of Physics, Johannes Gutenberg University Mainz, Germany — 2Faculty of Physics and Astronomy, Ruhr University Bochum, Germany — 3BioNTech SE, Mainz, Germany
Lipid-based nanoparticles and lipoplexes are successful nanocarriers for mRNA-based therapies. The molecular structure of these assemblies is still not fully understood. Lipoplexes including the ionizable lipid 2-dioleyloxy-N,N-dimethyl-3-aminopropane (DODMA), under specific conditions, have a pH-dependent lamellar structure, where lipid bilay- ers are separated by mRNA-rich layers. Here, the structure and dynamics of these lipoplexes are investigated at varying pH and mRNAconcentration using multiscale molecular dynamics simulations[1]. It is observed that the interaction between DODMA and RNA is slightly attractive only at low pH levels. This results into a pH-dependent relocation of the RNA inside the multilayers, from bilayer's surface at low pH to a more uniform distribution inside the hydrophilic slabs at high pH. Also, at high pH, DODMA lipids shift toward the hydrophobic part of the bilayer, thus increasing their leaflet-flipping rate, a phenomenon which may ultimately affect the fusion process of the lipoplex with the endosomal membrane.
[1] Settanni, G., Brill, W., Haas, H. and Schmid, F. (2022), Macromol. Rapid Commun. 43:2100683. https://doi.org/10.1002/marc.202100683