A DSC and FTIR spectroscopic study of the effects of the epimeric cholestan-3-ols and cholestan-3-one on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes: Comparison with their 5-cholesten analogs

Abstract

We present the results of a comparative differential calorimetric and Fourier transform infrared spectroscopic study of the effect of cholesterol and five analogs on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes. These sterols/steroids differ in both the nature and stereochemistry of the polar head group at C3 (β-OH, α-OH or C=O) and in the presence or absence of a double bond in ring B. In both the Δ(5) and saturated sterols/steroid series, the concentration of these compounds required to abolish the DPPC pretransition, inversely related to their relative ability to disorder gel state DPPC bilayers, decreases in the order β-OH > α-OH > C=O. However, in the saturated series, these concentrations are much more similar, regardless of polar head group chemical structure. Similarly, the residual enthalpy of the DPPC main phase transition at 50 mol% sterol/steroid, inversely related to the miscibility of these compounds in fluid DPPC bilayers, also increases in the order β-OH > α-OH > C=O, but this effect is again attenuated in the saturated series. Moreover, replacement of the double bond at C5 with a saturated linkage also reduces sterol/steroid solubility in all cases. Interestingly, the C5 double bond has no effect on DPPC hydrocarbon chain ordering in the βOH sterol pair, considerably increases ordering in the αOH pair, and considerably reduces ordering in the C=O pair. Moreover, the ability of these compounds to order the DPPC hydrocarbon chains decreases in the order β-OH > α-OH > C=O in the Δ(5) series of compounds, but in the order β-OH > C=O > α-OH in the saturated series. Our results indicate that the effects of the presence or absence of a double bond at C5 of ring B on the thermotropic phase behavior and organization of DPPC bilayers are influenced by the nature and stereochemistry of the polar group present at C3 and vice versa. Nevertheless, the characteristic effects of sterols/steroids on fluid lipid bilayers are optimal when an OH group rather than C=O group is present at C3, and when this OH group is in the equatorial (β) orientation. Moreover, the presence of a single double bond specifically at C5 is required to maximize sterol solubility in fluid DPPC bilayers, which is probably its primary function in natural sterols.

Monitoring the Transmembrane Proton Gradient Generated by Cytochrome bo3 in Tethered Bilayer Lipid Membranes Using SEIRA Spectroscopy

“…Also, the final molecule will be more stable because no stepwise oxidation of the double bond can cause its decomposition. Furthermore, dhChol has similar properties as Chol as was shown previously. − The two building blocks dhChol and TEGTs 2 were connected by a nucleophilic substitution of one tosyl functionality of TEGTs 2 by the deprotonated dhChol. The use of NaH in THF/DMF (1/1 v/v) finally gave WK3OTs in a satisfactory isolated yield of 50% (Scheme ).…”

Effects of Sterol-Like Additives on Phase Transition Behavior of Ion-Pair Amphiphile Bilayers

“…Moreover, lots of investigations 25 57 have been devoted to the effects of sterols especially CHOL , which are incorporated in lipid bilayers for modulating their characteristics, on the phase transition behavior, vesicular bilayer rigidity, and other properties by using various techniques such as DSC 25 55 57 . Among them, the well-known condensation effect of CHOL on lipid bilayers at a temperature above their main phase transition temperatures that is, lipid bilayers in the liquid-crystalline phase, L α , making the bilayer membranes more rigid was evidenced and documented 37,38,43,46,47,53 . On the other hand, the disordering effect of CHOL, which worked on lipid bilayers at a temperatures below their main phase transition temperatures that is, lipid bilayers in the gel phase, L β , making the bilayer membranes more fluidic was also evidenced and documented 37,38,46,47,53 .…”