Understanding the self-assembly and molecular structure of mRNA lipid nanoparticles at real size: Insights from the ultra-large-scale simulation

The largest simulated lipid nanoparticle (LNP) system reaches approximately 80 nm in diameter and encompasses around 30 million atoms.

• LNPs self-assemble into spherical structures within 50 nanoseconds under acidic pH conditions.
• LNPs exhibit a bicontinuous structure with both continuous lipid and aqueous phases.
• Lipid rafts formed by cholesterol and distearoylphosphatidyl choline enhance the rigidity and stability of LNPs.
• mRNA aggregation occurs independently of the lipid environment, suggesting varied interactions based on mRNA payloads.
• At neutral pH, lipid clustering may decrease the ability of LNPs to retain mRNA.

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