Cationic O-ethylphosphatidylcholines and their lipoplexes: phase behavior aspects, structural organization and morphology.
Ethylphosphatidylcholines, positively charged membrane lipid derivatives in which the anionic charge of the phosphate oxygen has been eliminated by ethylation, are promising nonviral, metabolizable transfection agents. We studied in detail the phase behavior, structural organization and morphology of the ethylphosphatidylcholines and their lipoplexes. Unlike the other phospholipids, dehydration does not change the melting transition temperature of O-ethyl-dipalmitoylphosphatidylcholine (EDPPC). Neither does an isoelectric amount of DNA, when added to the EDPPC aqueous dispersion. This is ascribed to the inability of EDPPC to form hydrogen bonds because of its headgroup modification. Similarly to its parent lipid DPPC, EDPPC displays a subtransition at 15 degrees C in its differential scanning calorimetry (DSC) heating scans after prolonged low-temperature incubation. The cooling behavior of the O-ethylphosphatidylcholines is sensitive to the thermal prehistory and the ionic strength. Different aggregate morphologies in the solid and the liquid-crystalline phases-respectively lamellar sheets and vesicles, as documented by light microscopy-are considered responsible for the cooling pattern. The interconversion between these morphologies is slow or even kinetically hindered, however, increasing the ionic strength to physiological values facilitates the conversion. The interdigitated chain arrangement of EDPPC gel phase tolerates incorporation of DNA between the bilayers. The minimum observed separation between the DNA strands is approximately 30-32 A, at DNA/lipid molar ratio > or =1. Formation of lipoplexes with DNA ordered in a 1-D lattice sandwiched between interdigitated lipid bilayers is reported for the first time.
Koynova
Rumiana
R
Department of Biochemistry, Molecular and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA. r-tenchova@northwestern.edu
MacDonald
Robert C
RC
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002412:Cations; D004247:DNA / Q000737:chemistry*; D000431:Ethanol; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular; D010713:Phosphatidylcholines / Q000737:chemistry*; D013816:Thermodynamics; D014961:X-Ray Diffraction
C476507:1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine; D002412:Cations; D008051:Lipid Bilayers; D008055:Lipids; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; D000431:Ethanol; D004247:DNA