A calorimetric and spectroscopic comparison of the effects of cholesterol and its sulfur-containing analogs thiocholesterol and cholesterol sulfate on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes

• Published in: Biochimica et biophysica acta Vol. 1858; no. 2; pp. 168 - 180
• Main Authors: Benesch, Matthew G.K., Lewis, Ruthven N.A.H., McElhaney, Ronald N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2016
• Subjects: 1,2-Dipalmitoylphosphatidylcholine; Calorimetry, Differential Scanning; Cholesterol; Cholesterol - analogs & derivatives; Cholesterol - chemistry; Cholesterol Esters - chemistry; Cholesterol sulfate; Dipalmitoylphosphatidylcholine; Humans; Lipid bilayer membranes; Lipid Bilayers - chemistry; Spectroscopy, Fourier Transform Infrared; Sterol/phospholipid interactions; Thiocholesterol; Sterol/phospholipid interactions; Chol; ΔT1/2; CholS; tChol; DSC; FTIR; Tm; Cholesterol sulfate; DMPC; Tp; DPPC; Dipalmitoylphosphatidylcholine; Thiocholesterol; Lipid bilayer membranes; SDPC; Pβ; Lo; ESR; Lα; SOPC; Lβ′ and Lβ; Cholesterol; NMR; PC; ΔH
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2015.11.006

We performed differential scanning calorimetric (DSC) and Fourier transform infrared (FTIR) spectroscopic studies of the effects of cholesterol (Chol), thiocholesterol (tChol) and cholesterol sulfate (CholS) on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine (DPPC) bilayer membranes. Our DSC results indicate that Chol and tChol incorporation produce small temperature increases in the main phase transition broad component while CholS markedly decreases it, but Chol decreases cooperativity and enthalpy more strongly than CholS and especially tChol. Hence, Chol and tChol thermally stabilize fluid DPPC bilayer sterol-rich domains while CholS markedly destabilizes them, and CholS and particularly tChol are less miscible in such domains. Our FTIR spectroscopic results indicate that Chol incorporation increases the rotational conformational order of fluid DPPC bilayers to a slightly and somewhat greater degree than tChol and CholS, respectively, consistent with our DSC findings. Also, Chol and CholS produce comparable degrees of H-bonding (hydration) of the DPPC ester carbonyls in fluid bilayers, whereas tChol increases H-bonding. At low temperatures, Chol is fully soluble in gel-state DPPC bilayers, whereas tChol and CholS are not. Thus tChol and CholS incorporation can produce considerably different effects on DPPC bilayers. In particular, the tChol thiol group markedly reduces its lateral miscibility and increases DPPC carbonyl H-bonding without significantly affecting the other characteristic effects of Chol itself, while the CholS sulfate group significantly reduces its ability to thermally stabilize and order fluid DPPC membranes. This latter result suggests that the molecular basis for the purported ability of CholS to “stabilize” various biological membranes should be re-examined. [Display omitted] •CholS produces larger decreases in the thermal stability of gel state DPPC bilayers than Chol or tChol.•Chol and tChol increase the thermal stability of fluid DPPC bilayers while CholS decreases it.•Chol is more laterally miscible in both gel and fluid DPPC bilayers than CholS and especially tChol.•Chol increases the hydrocarbon chain order of fluid DPPC bilayers to a greater extent than tChol and especially CholS.•Chol and CholS do not alter the degree of H-bonding of the DPPC carbonyl groups while tChol increases it.