Interactions between pH-sensitive liposomes and model membranes.
The structure and dynamics of two different pH-sensitive liposome systems were investigated by means of cryo-transmission electron microscopy and different photophysical techniques. Both systems consisted of dioleoylphosphatidylethanolamine (DOPE) and contained either oleic acid (OA) or a novel acid-labile polyethylene glycol-conjugated lipid (DHCho-MPEG5000) as stabiliser. Proton induced leakage, lipid mixing and structural changes were studied in the absence and presence of EPC liposomes, as well as in the presence of liposomes designed to model the endosome membrane. Neither DHCho-MPEG5000- nor OA-stabilised liposomes showed any tendency for fusion with pure EPC liposomes or endosome-like liposomes composed of EPC/DOPE/SM/Cho (40/20/6/34 mol.%). Our investigations showed, however, that incorporation of lipids from the pH-sensitive liposomes into the endosome membrane may lead to increased permeability and formation of non-lamellar structures. Taken together the results suggest that the observed ability of DOPE-containing liposomes to mediate cytoplasmic delivery of hydrophilic molecules cannot be explained by a mechanism based on a direct, and non-leaky, fusion between the liposome and endosome membranes. A mechanism involving destabilisation of the endosome membrane due to incorporation of DOPE, seems more plausible.
Bergstrand
Nill
N
Department of Physical Chemistry, Uppsala University, Box 579, S-751 23 Uppsala, Sweden. nill.bergstrand@fki.uu.se
Arfvidsson
Maria C
MC
Kim
Jong-Mok
JM
Thompson
David H
DH
Edwards
Katarina
K
D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000737:chemistry* / Q000648:ultrastructure; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D009391:Nephelometry and Turbidimetry; D019301:Oleic Acid / Q000737:chemistry; D010539:Permeability; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D010767:Phosphorylcholine; C075010:erucylphosphocholine; D019301:Oleic Acid; D011092:Polyethylene Glycols