Self-association Of Cholesterol Research Articles

Photophysical and Structural Characterization of Intrinsically Fluorescent Sterol Aggregates.

Self-association of cholesterol into aggregates and crystals is a hallmark of developing atherosclerosis. Intrinsically fluorescent sterols, such as dehydroergosterol (DHE), can be used to study sterol aggregation by fluorescence spectroscopy and microscopy, but a thorough understanding of DHE's photophysical and structural properties in the aggregated state is missing. Here, we show that DHE forms submicron fluorescent aggregates when evaporated from an ethanol solution. Using atomic force microscopy, we find that DHE, like cholesterol, forms compact oblate-shape aggregates of <100 nm in diameter. DHE's fluorescence is lowered in the aggregate compared to the monomeric form, and characteristic spectral changes accompany the aggregation process. Electronic structure calculations of DHE dimers in water indicate that Frenkel-type exciton coupling contributes to the lowered DHE fluorescence in the aggregates. Using molecular dynamics (MD) simulations, we show that DHE forms compact aggregates on the nanosecond scale and with strong intermolecular attraction, in which a broad range of orientations, and therefore electronic couplings, will take place. Tight packing of DHE in aggregates also lowers the apparent absorption cross section, further reducing the molecular brightness of the aggregates. Our results pave the way for systematic solubility studies of intrinsically fluorescent analogues of biologically relevant sterols.

Weak Intermolecular Associations and Anesthesia

Weak Intermolecular Associations and Anesthesia

Self-association of cholesterol in benzene and toluene solutions

The self-association of cholesterol in dilute benzene and toluene solutions was investigated by conventional infrared spectroscopy. The sample spectra, recorded in the fundamental OH stretching range, were resolved into the bands of functionally different OH groups of associated cholesterol and its predominant species identified by analysis of their absorbances. The formation constants of oligomers were derived from monomer absorbances measured as a function of cholesterol concentration. In addition to the monomers A 1, open à 2 (Δ H̃ 2=−11±1 kJ mol −1) and cyclic dimers  2 (Δ Ĥ 2=−24±2 kJ mol −1) in benzene and open dimers à 2 (Δ H̃ 2=−12±1 kJ mol −1) and tetramers A 4 (Δ H 4=−47±6 kJ mol −1) in toluene were established as the prevailing species.

Self-association of cholesterol in some chlorinated hydrocarbon solvents

The self-association of cholesterol in dilute solutions in 1,2-dichloroethane, trichloromethane and tetrachlorormethane and over the temperature range 298–328 K was investigated using conventional infrared spectroscopy. The information on the size of the predominant cholesterol species was obtained by numerical processing of the solution spectra, recorded in the fundamental OH stretching range. Formation constants were derived from monomer absorbances measured as a function of cholesterol concentration. The following prevailing species and their enthalpies of formation were established: the monomer A 1 and monomer-solvent complex A 1* (Δ H 1*=−9±3 kJ mol −1) in 1,2-dichloroethane; the monomer and open dimer ( Ã 2) (Δ H̃ 2=−15.0±1.2 kJ mol −1) in trichloromethane; the monomer, open trimer ( Ã 3) (Δ H̃ 3=−31±3 kJ mol −1) and cyclic hexamer ( Â 6) (Δ Ĥ 6=−70±10 kJ mol −1) in tetrachloromethane.

Hydrogen bonds between cholesterol and oxygen bases: a thermodynamic study

Using calorimetric and IR spectroscopic methods, the values of thermodynamic functions of (1 : 1) hydrogen-bond complex formation between cholesterol and some proton acceptors in CCl4 have been determined. The self-association of cholesterol in the solvent used was taken into account in calculations. The proton acceptors used are oxygen bases containing CO, —O—, PO and SO groups. The values of ΔfH were compared with those previously obtained for the pure bases. The enthalpy of hydrogen-bond complex formation of cholesterol is a linear function of Gutmann's donor number for all the proton acceptor compounds examined. Badger–Bauer's relation {ΔfH=f[Δv(OH)]} is not satisfied as well as ΔfH=f(DN) but it allows the prediction of values of enthalpy of complex formation between cholesterol and proton acceptors within ± 1.5 kJ mol–1 limits.

Dynamics of phosphatidylcholine-cholesterol mixed model membranes in the liquid crystalline state

The effects of cholesterol on the dynamics of cholestane spin probe (CSL) in various phosphatidylcholine-cholesterol mixed model membranes are examined. The lateral diffusion, D of CSL in DMPC/POPC/cholesterol ternary mixtures, is measured utilizing an improved dynamic imaging electron spin resonance method. It shows a factor of two decrease at 10 mol % and 25 degrees C, whereas it shows only a 40% decrease at 50 mol % and 50 degrees C. A comparison with results in POPC/cholesterol mixtures, which show a stronger effect of cholesterol on D, indicates that acyl chain unsaturation leads to stronger self association of cholesterol in PC model membranes. An S2CSL dependence of the activation energy for D, has been confirmed for the DMPC/POPC/cholesterol mixtures. Here SCSL is the order parameter for CSL. A similar correlation of R perpendicular, the perpendicular component of the rotational diffusion coefficient, with SCSL, which is true for all three mixtures (DMPC/cholesterol, POPC/cholesterol, and DMPC/POPC/cholesterol) we have studied, is also found. These are associated with the effects of enhanced local ordering on the free volume needed for translation and reorientation. Such correlations of dynamic properties D and R perpendicular with the thermodynamic quantity S, as well as the consistent interpretations of the effect of acyl chain unsaturation on the dynamics in terms of the activity coefficients, strongly emphasize the interrelation between the dynamic structure and the thermodynamics of the PC/cholesterol mixtures.

Dynamic imaging of lateral diffusion by electron spin resonance and study of rotational dynamics in model membranes. Effect of cholesterol

The effects of cholesterol on the dynamics and the structural properties of two different spin probes, the sterol type CSL and the phospholipid type 16-PC, in POPC/cholesterol oriented multilayer model membranes were examined. Our results are consistent with a nonideal solution containing cholesterol-rich clusters created by the self association of cholesterol in POPC model membranes. The lateral diffusion coefficient D of the spin probes was measured over the temperature range of 15 to 60 degrees C and over the concentration range of 0 to 30 mol% of cholesterol in the model membrane by the electron spin resonance (ESR) imaging method. The rotational diffusion coefficients (including R perpendicular) and the order parameter S were determined utilizing a nonlinear least square ESR spectral simulation method. D, R perpendicular and S of CSL deviate considerably from linear dependence on mole percent cholesterol. The D of CSL was decreased by a factor of four at 15 degrees C and a factor of two at 60 degrees C for concentrations of cholesterol over 10 mol %, whereas those of 16-PC were hardly affected. Cholesterol decreased R perpendicular by a factor of 10 at 30 mol % of cholesterol, but it increased slightly that of 16-PC. A significant increase of S for CSL due to the presence of cholesterol was observed. It is shown how the difference in variation of S for CSL vs. 16-PC with composition may be interpreted in terms of their respective activity coefficients, and how a single universal linear relation is obtained for the S of both probes in terms of a scaled temperature. Simple but general correlations of D and of R perpendicular with S were also found, which aid in the interpretation of these diffusion coefficients.

Self-association of cholesterol in nonaqueous solutions

Self-association of cholesterol in nonaqueous solutions

Self-Association of Cholesterol in Carbon Tetrachloride

Abstract Analysis of infrared hydroxyl multimer absorbances of dilute solutions of cholesterol in carbon tetrachloride as a function of the monomer absorbance strongly favours the interpretation of the association of this alcohol with a monomer-dimer-tetramer model up to a molar fraction of 0.012. This model also explains very well the concentration dependence of the apparent dipole moment. Equilibrium constants and dielectric parameters have been determined. Suggestions about the structure of the various associates are made.

Self-association of cholesterol in aqueous solution.

Cholesterol has a maximum solubility in aqueous solutions of 1.8 mug/ml or 4.7 muM. It undergoes a thermodynamically reversible self-association with a critical micelle concentration of 25 to 40 nM at 25 degrees . The cholesterol micelle is heterogeneous in size, probably rodlike in shape, and stabilized by an unusually high interaction energy between the aggregated monomers.

Self-association of cholesterol and its interaction with triglycerides. An infrared study.

Self-association of cholesterol and its interaction with triglycerides. An infrared study.