Surface Recognition and Complexations Between Synthetic Poly(ribo)nucleotides and Neutral Phospholipids and Their Implications in Lipofection

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 or surfactant-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 Mg 2+ and N-alkyl-N,N,N-trimetylammonium ions (CnTMA, n=12), regarding 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 the presence of divalent metal cations. Such an induced aggregation of vesicles either leads to heterogeneous multilamellar DNA-lipid arrangements, or to DNA-induced bilayer destabilization and lipid fusion. In contrast, stable monodispersed complexes are formed after compaction of DNA with surfactant, followed by the addition of vesicles. Surfactants bind to DNA in a cooperative manner and increased number of nucleic acid-bound C 12 TMA leads to a rise in the size of the resulting DNA-surfactant complexes, due to their aggregation. The formation of these bundles is governed by both elctrostatic and hydrophobic interactions of surfactant chains, the reaction being mediated by condensed counterions, steric hindrance or by intrinsic chain flexibility. In here, further employment of these polyelectrolyte nanostructures as an improved formulation in therapeutic gene delivery trials, as well as in DNA chromatography is discussed..