Effects of the structure of lipid-based agents in their complexation with a single stranded mRNA fragment: a computational study

In this work we employed fully atomistic molecular dynamics simulations, aiming towards a better understanding of the mechanisms associated with the formation and the stability of lipid-based RNA nanoassemblies, in an aqueous environment. We examined two groups of lipid-based complexation agents, differing in the degree of hydrophobicity and in the overall charge. The first group was comprised of cationic ionizable agents while the second included electrically neutral amphoteric phosphatidylcholine lipids. It was found that the overall charge of the complexation agents played the most decisive role in the energetics of the lipid/RNA association, while their degree of hydrophobicity affected their self-assembly and their complexation kinetics. The latter also affected the structural stability of the formed complexes since the water entrapped within the clusters of the less hydrophobic agents appeared to reduce the coherence of the lipid-RNA nanoassemblies. The combined effects of the aforementioned attributes dictated also the RNA conformation after complexation. The results from the present study provide thus new insight towards controlling the morphology, the energetic stability and the structural integrity of the formed complexes.