RNA adsorption dynamics onto membrane models for lipid nanoparticles

MONJE-GALVÁN, VIVIANA; RAMÍREZ, RICARDO X.; FELSZTYNA, IVÁN; KANDUC, MATEJ; GUZMÁN, HORACIO V.

Pennsylvania

Congreso; 2024 Biophysical Society Annual Meeting; 2024

Biophysical Society

RNA is a functionally rich molecule with multilevel, hierarchical structures and complex dynamics in the presence of different substrates (1). Lipid nanoparticles (LNPs) are particularly promising as mRNA delivery medium due to their remarkable ability to transport genetic material to targeted cells. Yet, the design of LNPs remains challenging (2,3), owing to poorly understood mechanisms and factors that modulate RNA and LNP adsorption to membranous substrates.This is an exhaustive all-atom molecular dynamics study of the influence of membrane composition on the adsorption behavior and conformation of a single stranded RNA fragment. We used five distinct membrane models with lipid composition selected from commercially available LNPs to account for (i) surface charge, (ii) topological features, (iii) unsaturation degree of the fatty acid tails, and (iv) cholesterol content (4-7).