Association of polynucleotides with nucleolipid bilayers driven by molecular recognition

This contribution reports on the interaction of ss-polynucleotides of various length and sequence with liposomal dispersions of anionic lipids. No appreciable structural and morphological variations were detected for POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-glycerol) liposomes, as expected from the high negative charge density both of liposomal surface and of the poly or oligonucleotide. Conversely, when similarly charged POPN nucleolipids (1-palmitoyl-2-oleoylphosphatidyl-nucleosides) were used, meaningful differences could be observed both on size and morphology of the mixed aggregates. The comparison with POPG/nucleic acids mixed systems points to the conclusion that the driving force for association of nucleolipid liposomes with nucleic acids can be ascribed to selective interactions at the polar head level which overcome electrostatic repulsion. Dynamic light scattering, Cryo-TEM and circular dichroism provided an ensemble of results where an interesting dependence on the polynucleotide base nature and contour length emerges. The extent of interaction can be modulated, in terms of size of the complexes, by choice of background buffer, ionic strength and polynucleotide length.

Graphical abstractComplexes formed by single strand DNA with anionic nucleolipid vesicles.Figure optionsDownload full-size imageDownload high-quality image (108 K)Download as PowerPoint slideHighlights► Anionic nucleolipid vesicles associate with nucleic acids. ► The structure of the complexes depends on the buffer kind and ionic strength. ► A dependence on the nucleotide sequence is also observed. ► Shorter oligonucleotides produce larger complexes than polynucleotides. ► These results can find application in the design of formulations for DNA delivery.