Chiral DNA packaging in DNA-cationic liposome assemblies.
Recent studies have indicated that the structural features of DNA-lipid assemblies, dictated by the lipid composition and cationic lipid-to-DNA ratio, critically affect the efficiency of these complexes in acting as vehicles for cellular delivery of genetic material. Using circular dichroism we find that upon binding DNA, positively-charged liposomes induce a secondary conformational transition of the DNA molecules from the native B form to the C motif. Liposomes composed of positively-charged and neutral 'helper' lipids, found to be particularly effective as transfecting agents, induce - in addition to secondary conformational changes - DNA condensation into a left-handed cholesteric-like phase. A structural model is presented according to which two distinct, yet inter-related modes of DNA packaging coexist within such assemblies. The results underline the notion that subtle changes in the components of a supramolecular assembly may substantially modulate the interplay of interactions which dictate its structure and functional properties.
Zuidam
N J
NJ
Department of Biochemistry, The Hebrew University, Hadassah Medical School, P.O. Box 12272, Jerusalem, Israel. nicolaas@cc.huji.il
Barenholz
Y
Y
Minsky
A
A
D002412:Cations; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D009994:Osmolar Concentration; D010714:Phosphatidylethanolamines / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013237:Stereoisomerism
D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C094877:dioleoyl phosphatidylethanolamine; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane