ssRNA base pairing at a bilayer interface can be controlled by the acyl chain order

Abstract

RNA–lipid interactions are central to structure and function in biological systems as well as to the development of new applications in medicine and biotechnology. We have studied adsorption and base pairing of short RNA oligonucleotides at model lipid membranes with different compositions by means of QCM-D, confocal microscopy and ITC. The major finding is that base pairing of short complementary RNA strands can be controlled by the acyl-chain chain order, i.e. chains in the solid vs. liquid state, in a deposited bilayer. It was shown that the base pairing with a complementary strand ssRNA takes place at the bilayer when the first strand is pre-adsorbed to a bilayer with solid chains, but not when the first strand is pre-adsorbed to a liquid crystalline bilayer with fluid chains. The results imply that the ssRNA hydrophobic bases are not accessible to the complementary strand bases when RNA is adsorbed to a fluid bilayer, which can be due to hydrophobic interactions with the apolar layer in the fluid bilayer. It is also likely that the difference in lipid phase behaviour affects the kinetics for the base pair reaction at the surface. The corresponding base pairing experiment at the interface of a soft cationic polymer layer consisting of poly(amido amine) PAMAM dendrimers of generation 4 yielded similar results. RNA and DNA were found to adsorb to mixed bilayers that contain the naturally occurring cationic lipid sphingosine as well as to bilayers that contain more conventional surfactants, and it is found that the surface with adsorbed nucleic acid is close to electroneutral at saturation.