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BP: Fachverband Biologische Physik
BP 4: Computational Biophysics I
BP 4.11: Vortrag
Montag, 18. März 2024, 17:45–18:00, H 0112
Cationic and anionic lipid mixing favors the lamellar-to-hexagonal phase transition in coarse-grained molecular dynamics simulations — •David Noel Zimmer1,2, Friederike Schmid1, and Giovanni Settanni1,2 — 1Physics Department Johannes Gutenberg University Mainz — 2Faculty of Physics and Astronomy Ruhr University Bochum
Lipid-based nanoparticles (LNPs) are used as delivery vehicles for RNA-therapeutics, a potentially broad class of drugs including COVID-19 vaccines as well as drugs against genetically inherited diseases and cancer. LNPs are produced by rapid mixing the cargo RNA at low pH with a lipid formulation containing ionizable cationic lipids, helper and PEGylated lipids. The lipid formulation helps to compact the RNA, to screen it from degradation and to deliver it to the target cell. LNPs' mechanisms of action is not yet well understood. Here, we use coarse-grained molecular dynamics simulation to investigate the effect of the fusion process between the LNP and the endosomal membrane following cellular uptake of the LNP. The simulations show that the mixing of the anionic lipids of the endosome with the cationic lipids of the LNP leads to a stabilization of the hexagonal phase versus the lamellar phase. Analysis of the hexagonal phase shows that cationic lipids tend to accumulate in the space between three adjacent tubules, while anionic lipids distribute more uniformly around the tubules, indicating a lack of correlation in the position of the two oppositely charged lipids.
Keywords: Lipid-based nanoparticles; RNA delivery; ionizable cationic lipids; lamellar/hexagonal phase transition; molecular dynamics simulations