Cholesterol displacement from membrane phospholipids by hexadecanol.
Adding cholesterol to monolayers of certain phospholipids drives the separation of liquid-ordered from liquid-disordered domains. The ordered phases appear to contain stoichiometric complexes of cholesterol and phospholipid. Furthermore, it has been suggested that the cholesterol in these complexes has a low chemical activity compared to that of the free sterol; i.e., that in excess of the phospholipid binding capacity. We have now tested the hypothesis that the membrane intercalator 1-hexadecanol (HD) similarly associates with phospholipids and thereby displaces the complexed cholesterol. HD introduced into monolayers of pure dimyristoylphosphatidylcholine generated highly condensed (stable and solid) domains. In contrast, the phase behavior of mixed monolayers of the phospholipid, sterol, and alcohol suggested that HD could substitute for cholesterol mole for mole in promoting liquid-ordered domains. We also found that the transfer of cholesterol from mixed monolayers to aqueous cyclodextrin was greatly stimulated by the presence of HD, but only at levels sufficient to competitively displace the sterol from the phospholipid. This enhanced efflux was interpreted to reflect an increase in uncomplexed cholesterol. We conclude that HD forms complexes with dimyristoylphosphatidylcholine that are surprisingly similar to those of cholesterol. HD competitively displaces cholesterol from the phospholipid and thereby increases its chemical activity.
Ratajczak
Maria K
MK
Department of Physics, Institute for Biophysical Dynamics and James Franck Institute, The University of Chicago, Chicago, IL 60637, USA.
Ko
Y T Chris
YT
Lange
Yvonne
Y
Steck
Theodore L
TL
Lee
Ka Yee C
KY
D055592:Biophysical Phenomena; D001703:Biophysics; D004083:Cholestanol / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry* / Q000494:pharmacology; D006874:Hydrostatic Pressure; D007700:Kinetics; D008563:Membrane Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D010743:Phospholipids / Q000737:chemistry*; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry
D005233:Fatty Alcohols; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010743:Phospholipids; D047392:beta-Cyclodextrins; D004083:Cholestanol; C005031:cetyl alcohol; D002784:Cholesterol; C031215:betadex; D004134:Dimyristoylphosphatidylcholine