RNA and DNA interactions with zwitterionic and charged lipid membranes — A DSC and QCM-D study

Abstract

The aim of the present study is to establish under which conditions tRNA associates with phospholipid bilayers, and to explore how this interaction influences the lipid bilayer. For this purpose we have studied the association of tRNA or DNA of different sizes and degrees of base pairing with a set of model membrane systems with varying charge densities, composed of zwitterionic phosphatidylcholines (PC) in mixtures with anionic phosphatidylserine (PS) or cationic dioctadecyl-dimethyl-ammoniumbromide (DODAB), and with fluid or solid acyl-chains (oleoyl, myristoyl and palmitoyl). To prove and quantify the attractive interaction between tRNA and model-lipid membrane we used quartz crystal microbalance with dissipation (QCM-D) monitoring to study the tRNA adsorption to deposit phospholipid bilayers from solutions containing monovalent (Na(+)) or divalent (Ca(2+)) cations. The influence of the adsorbed polynucleic acids on the lipid phase transitions and lipid segregation was studied by means of differential scanning calorimetry (DSC). The basic findings are: i) tRNA adsorbs to zwitterionic liquid-crystalline and gel-phase phospholipid bilayers. The interaction is weak and reversible, and cannot be explained only on the basis of electrostatic attraction. ii) The adsorbed amount of tRNA is higher for liquid-crystalline bilayers compared to gel-phase bilayers, while the presence of divalent cations show no significant effect on the tRNA adsorption. iii) The adsorption of tRNA can lead to segregation in the mixed 1,2-dimyristoyl-sn-glycerol-3-phosphatidylcholine (DMPC)-1,2-dimyristoyl-sn-glycero-3-phosphatidylserine (DMPS) and DMPC-DODAB bilayers, where tRNA is likely excluded from the anionic DMPS-rich domains in the first system, and associated with the cationic DODAB-rich domains in the second system. iv) The addition of shorter polynucleic acids influence the chain melting transition and induce segregation in a mixed DMPC-DMPS system, while larger polynucleic acids do not influence the melting transition in these system. The results in this study on tRNA-phospholipid interactions can have implications for understanding its biological function in, e.g., the cell nuclei, as well as in applications in biotechnology and medicine.

The role of long noncoding RNAs in cancer metastasis

“…These observations also raise questions as to whether lncRNAs can recruit adaptor proteins such as GRB2 to the vicinity of the carboxy-termini of membrane-bound receptors containing SH2 domains, which are responsible for the direct modulation of RTK-mediated cell signaling cascades. These observations also support an earlier hypothesis from studies on RNA viruses, concerning RNA-lipid interactions, specifically those with charged moieties including phosphatidylcholine (PC) and phosphatidylserine (PS), are crucial in supporting life [99][100][101][102] . Further work is warranted to elucidate the complexities of these lncRNAs that operate as trans regulators of cell signaling pathways.…”

Membrane potential-dependent binding of polysialic acid to lipid monolayers and bilayers

“…The formation of equilibrium clusters composed of positively charged liposomes stuck together by a polyanionic polyacrylate was demonstrated [45]. The adsorption of tRNA on the surface of lipid bilayers can lead to segregation in the mixed anionic or cationic bilayers, where tRNA is likely excluded from the anionic-rich domains in the first system, and associated with the cationic-rich domains in the second system [46]. Conditions such as the lipid composition of liposomes and salt concentration, under which DNA is still physically associated with positively charged liposomes, were previously studied [47].…”

microRNAs in lipoprotein and lipid metabolism: from biological function to clinical application

“…Interestingly, sphingomyelin (SM) binds RNA and prevents its degradation by RNAses [139,140]. Moreover, a few groups have reported that small RNAs could bind to phospholipid membranes using vesicular models [141][142][143][144]. Whether the plasma membrane SM, enriched into lipid rafts, could also bind miRNA and contribute to its export to HDLs has not been published so far.…”