A comparative differential scanning calorimetry study of the effects of cholesterol and various oxysterols on the thermotropic phase behavior of dipalmitoylphosphatidylcholine bilayer membranes. (February 2016)

• Record Type: Journal Article
• Authors: Benesch, Matthew G.K.; McElhaney, Ronald N.
• Is Part Of: Chemistry and physics of lipids. Volume 195(2016)
• Page Start: 21
• Page End: 33
• Publication Date: 2016-02
• Subjects: C cholesterol (5-cholestene-3β-ol) -- 4β-HC 4β-hydroxycholesterol (5-cholesten-3β, 4β-diol) -- 7α-HC 7α-hydroxycholesterol (5-cholesten-3β, 7α-diol) -- 7β-HC 7β-hydroxycholesterol (5-cholesten-3β, 7β-diol) -- 25-HC 25-hydroxycholesterol (5-cholesten-3β, 25-diol) -- 5α, 6β-HC 5α, 6β-hydoxycholesterol (cholestan-3β, 5α, 6β-triol) -- 7-KC 7-ketocholesterol (5-cholesten-3β-ol-7-one) -- 5α, 6α-EC 5α, 6α-epoxycholesterol (cholestan-5α, 6α-epoxy-3β-ol) -- 5β, 6β-HC 5β, 6β-epoxycholesterol (cholestan-5β, 6β-epoxy-3β-ol) -- PC phosphatidylcholine -- DPPC dipalmitoyophosphatidylcholine -- DSC differential scanning calorimetry -- Tp the pretransition temperature maximum -- Tm the main transition temperature maximum -- ΔH the transition enthalpy -- ΔT½ the width of the phase transition at half height, inversely related to the cooperativity of the phase transition (the superscripts "shp" and "brd" appended to these thermodynamic parameters refer to the sharp and broad components of the main phase transition of sterol-containing DPPC bilayers, respectively) -- Lβ' and Lβ lamellar gel phases with tilted and untilted hydrocarbon chains, respectively -- Pβ' rippled gel phase with tilted hydrocarbon chains -- Lα lamellar liquid-crystalline phase -- Lo lamellar liquid-ordered phase; Cholesterol -- Oxysterols -- Dipalmitoylphosphatidylcholine -- Sterol/phospholipid interactions -- Lipid bilayer membranes -- Thermotropic phase behavior; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipids; Periodicals; Electronic journals; 547.77
• DOI: 10.1016/j.chemphyslip.2015.11.003
• Languages: English
• ISSNs: 0009-3084

Abstract

Highlights: Oxysterols reduce the temperature ( T ), cooperativity ( C ) and enthalpy (Δ H ) of the DPPC pretransition more than cholesterol. Oxysterols reduce the T, but not the C or Δ H, of the sharp component of the DPPC main phase transition more than cholesterol. Oxysterols reduce the T more, but the C and Δ H of the broad component of the DPPC main phase transition less, than cholesterol. Oxysterols reduce the stability and order of both gel and fluid DPPC bilayers more, but are less miscible in them, than cholesterol. The cholesterol-like effects of various oxysterols on DPPC bilayer membranes generally decrease as their polarity increases. Abstract: We have carried out a comparative differential scanning calorimetric (DSC) study of the effects of cholesterol (C) and the eight most physiologically relevant oxysterols on the thermotropic phase behavior of dipalmitoylphosphatidylcholine (DPPC) bilayer membranes. The structures of these oxysterols differ from that of C by the presence of additional hydroxyl, keto or epoxy groups on the steroid ring system or by the presence of a hydroxyl group in the alkyl side chain. In general, the progressive incorporation of these oxysterols reduces the temperature, cooperativity and enthalpy of the pretransition of DPPC to a greater extent than C, indicating that their presence thermally destabilizes and disorders the gel states of DPPC bilayers to a greater extent than C. Similarly, the incorporation of these oxysterols either increases the temperature of the broad component of the main phase transition to a smaller extent than C or actually decreases it. Again, this indicates that the presence of these compounds is less effective at thermally stabilizing and ordering the sterol-rich domains of DPPC bilayers than is C itself. Moreover, the incorporation of these oxysterols decrease the cooperativity and enthalpy of the main phase transition of DPPC to a smaller extent than C, indicating that they are somewhat less miscible in fluid DPPC bilayers than is C. Particularly notable in this regard is 25-hydroxycholesterol, which exhibits a markedly reduced miscibility in both gel and fluid DPPC bilayers compared to C itself. In general, the effectiveness of these oxysterols in stabilizing and ordering DPPC bilayers decreases as their rate of interbilayer exchange and the polarity of the oxysterol increases. We close by providing a tentative molecular explanation for the results of our DSC studies and of those of previous biophysical studies of the effects of various oxysterol on lipid bilayer model membranes.