RNA Order Regulates\nIts Interactions with Zwitterionic\nLipid Bilayers

RNA–lipid interactions directly influence RNA\nactivity,\nwhich plays a crucial role in the development of new applications\nin medicine and biotechnology. However, while specific preferential\nbehaviors between RNA and lipid bilayers have been identified experimentally,\ntheir molecular origin remains unexplored. Here we use molecular dynamics\nsimulations to investigate the interaction between RNA and membranes\ncomposed of zwitterionic lipids at the atomistic level. Our data reproduce\nand rationalize previous experimental observations, including that\nshort-chain RNAs rich in guanine have a higher affinity for gel-phase\nmembranes compared to RNA sequences rich in other nucleotides and\nthat RNA prefers gel-phase membranes to fluid bilayers. Our simulations\nreveal that RNA order is a key molecular determinant of RNA–zwitterionic\nphospholipid interactions. Our data provide a wealth of information\nat the atomic level that will help accelerate research on RNA–lipid\nassemblies for task-specific applications such as designing lipid-based\nnanocarriers for RNA delivery.