Phospholipid-Nucleic Acid Complexation: Biomolecular Energetics of DNA-Mg2+-Phosphatidylcholine Ternary Complex Formation, Compaction and Relevance as Lipoplex Formulation

Abstract

Thermodynamic features related to preparation and use of self-assemblies formed between multilamellar and unilamellar zwitterionic liposomes and polynucleotides with various conformation and sizes are presented. The divalent metal cation induced adsorption, aggregation and adhesion between single- and double-stranded polyribonucleotides and phosphatidylcholine vesicles was followed by differential adiabatic scanning microcalorimetry. Nucleic acid condensation and compaction mediated by Mg2+ was followed, with regard to interfacial interaction with unilamellar vesicles. Microcalorimetric measurements of synthetic phospholipid vesicles and poly(ribo)nucleotides and their ternary complexes with inorganic cations were used to build the thermodynamic model of their structural transitions. The increased thermal stability of the phospholipid bilayers is achieved by affecting their melting transition temperature by nucleic acid induced electrostatic charge screening. Measurements give evidence for the stabilization of polynucleotide helices upon their association with liposomes in presence of divalent metal cations. Such an induced aggregation vesicles either leads to heterogeneous multilamellar DNA-lipid arrangements, or to DNA-induced bilayer destabilization and lipid fusion. The further employment of these polyelectrolyte nanostructures as an improved formulations in therapeutic gene delivery trials, as well as in DNA chromatography is discussed.