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Poly(ethylene glycol)‐lipid conjugates inhibit phospholipase C‐induced lipid hydrolysis, liposome aggregation and fusion through independent mechanisms
Author(s) -
Basáñez Gorka,
Goñi Félix M,
Alonso Alicia
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00716-3
Subject(s) - liposome , vesicle , chemistry , ethylene glycol , peg ratio , phosphatidylethanolamine , lipid bilayer fusion , hydrolysis , phospholipid , lipid bilayer , bilayer , vesicle fusion , biophysics , phospholipase , chromatography , biochemistry , membrane , organic chemistry , enzyme , phosphatidylcholine , biology , finance , synaptic vesicle , economics
Poly(ethylene glycol)‐phosphatidylethanolamine (PEG‐PE) conjugates have been introduced in liposomal compositions. The resulting large unilamellar vesicles were subjected to the action of phospholipase C. Enzyme‐promoted vesicle aggregation and fusion were assayed in liposomes containing various proportions of PEG‐PE. At PEG‐PE concentrations above 1 mol% the rate of phospholipid hydrolysis decreases, perhaps because the PEG moiety hinders the enzyme from reaching the membrane surface. At concentrations above 0.1 mol% vesicle aggregation occurs at a slower rate, presumably because of the repulsive barrier properties or surface‐grafted PEG. Lipid mixing decreases in parallel with vesicle aggregation. Finally, liposomal fusion rates measured as mixing of vesicle aqueous contents are decreased at or even below 0.1 mol%. The latter inhibition is due, apart from the reduced rates of lipid hydrolysis, vesicle aggregation and lipid mixing, to a PEG‐PE‐based stabilization of the lipid bilayer structure. Thus the observed low rates of contents mixing arise from three combined and independent inhibitory effects of PEG‐PE.