Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently
Autor: | Robert C. MacDonald, Rumiana Koynova |
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Jazyk: | angličtina |
Předmět: |
Membrane lipids
Static Electricity Biophysics 02 engineering and technology Transfection Biochemistry Article Membrane Lipids 03 medical and health sciences chemistry.chemical_compound Animals Fluorometry Lipid bilayer phase behavior Lipid phase transition Lipid bilayer 030304 developmental biology Phosphatidylethanolamine 0303 health sciences Liposome Bilayer Hexagonal phase Surface charge Biological membrane DNA Cell Biology 021001 nanoscience & nanotechnology Lipids Cationic lipid chemistry Liposomes Cattle lipids (amino acids peptides and proteins) DNA unbinding 0210 nano-technology |
Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. (10):2373-2382 |
ISSN: | 0005-2736 |
DOI: | 10.1016/j.bbamem.2007.04.026 |
Popis: | A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids. Here we report our finding that lipid mixtures mimicking biomembrane lipid compositions are superior to pure anionic liposomes in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes), even though they have a much lower negative charge density (and thus lower capacity to neutralize the positive charge of the lipoplex lipids). Flow fluorometry revealed that the portion of DNA released after a 30-min incubation of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic phosphatidylserine or phosphatidylglycerol was 19% and 37%, respectively, whereas a mixture mimicking biomembranes (MM: phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine /cholesterol 45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%, respectively, of the DNA content. A possible reason for this superior power in releasing DNA by the natural lipid mixtures was suggested by structural experiments: while pure anionic lipids typically form lamellae, the natural lipid mixtures exhibited a surprising predilection to form nonlamellar phases. Thus, the MM mixture arranged into lamellar arrays at physiological temperature, but began to convert to the hexagonal phase at a slightly higher temperature, approximately 40-45 degrees C. A propensity to form nonlamellar phases (hexagonal, cubic, micellar) at close to physiological temperatures was also found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). This result reveals that electrostatic interactions are only one of the factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers to form nonlamellar phases has been described in terms of bilayer "frustration" which imposes a nonzero intrinsic curvature of the two opposing monolayers. Because the stored curvature elastic energy in a "frustrated" bilayer seems to be comparable to the binding energy between cationic lipid and DNA, the balance between these two energies could play a significant role in the lipoplex-membrane interactions and DNA release energetics. |
Databáze: | OpenAIRE |
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