CHOLESTEROL VERSUS CHOLESTEROL SULFATE - EFFECTS ON PROPERTIES OF PHOSPHOLIPID-BILAYERS CONTAINING DOCOSAHEXAENOIC ACID

The important omega-3 fatty acid docosahexaenoic acid (DHA) is present at high concentration in some membranes that also contain the unusual sterol cholesterol sulfate (CS). The association between these lipids and their effect on membrane structure is presented here. Differentia l scanning calorimetry (DSC), MC540 fluorescence, erythritol permeabil ity, pressure/area isotherms on lipid monolayers and molecular modelin g are used to compare the effect of CS and cholesterol on model phosph olipid membranes. By DSC, CS decreases the main phase transition tempe rature and broadens the transitions of dipalmitolyphosphatidylcholine (DPPC), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (18:0,18:1 PC) and royl-2-docosahexaenopl-sn-glycero-3-phosphocholine (18:0,22:6 PC) to a much larger extent than does cholesterol. In addition CS produce s a three-component transition in 18:0,18:1 PC bilayers that is not se en with cholesterol. In a mixed phospholipid bilayer composed of 18:0, 18:1 PC/18:0,22:6 PC (1:1, mol/mol), CS at 2.5 membrane mol% or more i nduces lateral phase separation while cholesterol does not. CS decreas es lipid packing density and increases permeability of 18:0,18:1 PC an d 18:0,22:6 PC bilayers to a much larger extent than cholesterol. CS d isrupts oleic acid-containing bilayers more than those containing DHA. Molecular modeling confirms that the anionic sulfate moiety on CS ren ders this sterol more polar than cholesterol with the consequence that CS likely resides higher (extends further into the aqueous environmen t) in the bilayer. CS can therefore be preferentially accommodated int o DHA-enriched bilayers where its tetracyclic ring system may fit into the Delta 4 pocket of DHA, a location excluded to cholesterol. It is proposed that CS may in part replace the membrane function of choleste rol in DHA-rich membranes. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.