Comparison of steady-state fluorescence polarization and urea permeability of phosphatidylcholine and phosphatidylsulfocholine liposomes as a function of sterol structure.
The well-known reduction in the permeability properties of liposomes of dimyristoylphosphatidylcholine (DMPC) by sterols has also been demonstrated for its sulfonium analog (DMPSC) in which the N+(CH3)3 group of choline is replaced by S+(CH3)2. We have now compared the effects of 25 mol% 24-methylenecholesterol and cholesterol on the initial rates of urea permeation into dipalmitoyl-PC (DPPC) and dipalmitoyl-PSC (DPPSC) liposomes above the gel-to-liquid-crystalline phase transition temperature and found a greater reduction with 24-methylenecholesterol/DPPSC than with cholesterol/DPPSC liposomes but little difference between the two sterols in DPPC liposomes. Fluorescence polarization studies, using diphenylhexatriene as a probe, show that polarization (P) values are considerably higher in DMPSC liposomes containing 20 and 30 mol% 24-methylenecholesterol than in DMPC liposomes containing 20 and 30 mol% cholesterol. Higher P values were also obtained in DMPSC liposomes containing other 24-alkyl-substituted sterols (beta-sitosterol, ergosterol and campesterol) than in DMPC liposomes containing the same sterols. Reduced permeability rates in PSC liposomes containing 24-alkyl-substituted sterols are correlated with higher polarization values, reflecting an increased degree of order and/or motion in these liposomes compared with liposomes from the corresponding PC. These results suggest that alkyl substitution at C-24 of the sterol molecule results in tighter interactions with the sulfonium analog of PC than with PC.
Pugh
E L
EL
Department of Biochemistry, University of Ottawa, Ontario, Canada.
Bittman
R
R
Fugler
L
L
Kates
M
M
D002784:Cholesterol / Q000031:analogs & derivatives / Q000494:pharmacology; D005454:Fluorescence Polarization; D008081:Liposomes / Q000032:analysis*; D010539:Permeability; D010713:Phosphatidylcholines / Q000032:analysis*; D013261:Sterols / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000032:analysis*
D008081:Liposomes; D010713:Phosphatidylcholines; D013261:Sterols; C033841:phosphatidylsulfocholine; D014508:Urea; D002784:Cholesterol; C002537:24-methylenecholesterol