Against Expectations: Unassisted RNA Adsorption onto Negatively Charged Lipid Bilayers

The composition and physicochemical properties of biological membranes can be altered by diverse membrane integral and peripheral proteins as well as by small molecules, natural and synthetic. Diverse oligonucleotides have been shown to electrostatically interact with cationic and bivalent ion loaded zwitterionic liposomes, leading to the formation of oligonucleotide-liposome aggregates. However, interaction of RNAs with other membrane surfaces remains ill understood. We used the nonnatural RNA10 to investigate RNA binding to anionic and net-uncharged membrane surfaces. RNA10 had initially been selected in a screen for nonnatural RNA motives that bind to phosphatidylcholine liposomes in the presence of Mg²⁺. Here we show that interaction of defined RNA molecules with membrane surfaces crucially depends on electrostatic surface properties. Furthermore, RNA10 electrostatically binds to anionic lipid bilayers in the absence of Mg²⁺ or other bivalent cations, and this interaction leads to measurably changed physicochemical properties of the bilayer and the oligonucleotide. Thus, the structure of polyanionic RNA can be modulated via contact with negatively charged membrane surfaces and vice versa.