Details

Autor(en) / Beteiligte

• Yan, Jiang
• Berezhnoy, Nikolay V.
• Korolev, Nikolay
• Su, Chun-Jen
• Nordenskiöld, Lars

Titel

Structure and internal organization of overcharged cationic-lipid/peptide/DNA self-assembly complexes

Ist Teil von

• Biochimica et biophysica acta, 2012-07, Vol.1818 (7), p.1794-1800

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• The combination of cationic lipids with cationic peptides and DNA vectors can produce synergistic effects in gene delivery to eukaryotic cells. Binary complexes of cationic lipids with DNA are well-studied whereas little information is available about the structure of the ternary lipid/peptide/DNA (LPD) complexes and mechanisms defining DNA protection and delivery. Here we use synchrotron small angle X-ray scattering and dynamic light scattering zeta-potential measurements to determine structure and the net charge of supramolecular aggregates of complexes in mixtures of plasmid DNA, cationic liposomes formed from DOTAP, plus a linear cationic ε-oligolysine with the pendant α-amino acids Leu-Tyr-Arg (LYR), ε-(LYR)K10. These ternary complexes display multilamellar structures with relatively constant separation between DOTAP bilayers, accommodating a hydrated monolayer of parallel DNA rods. The DNA–DNA distance in the complexes varies as a function of the net positive to negative (lipid+peptide)/DNA charge ratio. An explanation for the observed dependence of DNA–DNA distance on charge ratio was proposed based on general polyelectrolyte properties of non-stoichiometric polycation–DNA mixtures. ► Lamellar lipid/ε-peptide/DNA complex contains DNA monolayer and lipid bilayer. ► ε-peptides insert between parallel DNA and are present on particle surface. ► DNA–DNA distance (dDNA) depends on total positive to negative charge ratio. ► The dependence is explained by an electrostatic analysis. ► Variation of surface potential has a similar tendency as the change in dDNA.