Anisotropic Motion and Molecular Dynamics of Cholesterol, Lanosterol, and Ergosterol in Lecithin Bilayers Studied by Quasi-elastic Neutron Scattering

Abstract

Quasi-elastic neutron scattering (QENS) was employed to study the molecular dynamics of three structurally related sterols, namely, cholesterol, lanosterol, and ergosterol. Oriented bilayers of dipalmitoylphosphatidylcholine (DPPC) were investigated at 40 mol % sterol content and at three temperatures (20, 36, and 50 degrees C) for two energy resolutions. Data analysis was concentrated on a direct comparison of the out-of-plane and the in-plane high-frequency motions of the three sterols in terms of their rates and amplitudes. The (spatially restricted) diffusive motion of the three sterols in the two directions was characterized by diffusion constants in the range of (5-30) x 10(-12) x m(2) x s(-1), with a significantly faster rate of diffusion along the membrane normal, resulting in a diffusional anisotropy, D(a). At low temperature (20 degrees C), cholesterol showed the highest value (D(a) = 4.5), while lanosterol gave the lowest one (D(a) = 2.0). At high temperature (50 degrees C), ergosterol diffusion had the highest diffusion anisotropy (D(a) = 2.0) compared to lanosterol (D(a) = 1.8) and cholesterol (D(a) = 1.6). Most interestingly, cholesterol showed at all three temperatures an amplitude of its out-of-plane-motion of 1.0-1.1 nm, more than a factor of 3 higher than measured for the other two sterols. This finding suggests that the short alkyl chain of the cholesterol molecule may cross at high frequency the bilayer midplane, while the other two sterols remain confined within the geometrical limits of each monolayer leaflet. The results provide an example of how slight structural alterations of sterols can affect their molecular dynamics in bilayers, which in turn may be relevant to the membrane micromechanical properties.

The Potential of Fluorescent and Spin-labeled Steroid Analogs to Mimic Natural Cholesterol

“…It is known that cholesterol molecules assume an upright position in the membrane with the polar OH group facing the aqueous phase (37). Due to the high mobility in the liquid crystalline phase, a distribution of the steroid parallel to the membrane normal has been observed and attributed to out of plane motions for the sterol (38). In the current study, the width of this distribution was determined by 1 H MAS NOESY.…”

“…Accordingly, cholesterol molecules are also subject to various types of motions (57). In particular, transverse motions of large amplitude have been observed for cholesterol by neutron scattering data (38). Therefore, the location of cholesterol segments parallel to the membrane normal is best described by broad distribution functions.…”

Investigating the membrane orientation and transversal distribution of 17β-estradiol in lipid membranes by solid-state NMR

“…Although the chemical structure of E 2 is related to the structure of cholesterol, the interactions between these sterols and membrane phospholipids are quite different. It was already shown that other cholesterol related molecules such as fluorescent cholesterol analogues or cholesterol precursors fail to produce such pronounced condensation effects as natural cholesterol (Scheidt et al, 2003;Huster et al, 2005;Oradd et al, 2009;Endress et al, 2002;Vogel et al, 2009). This is induced by relatively small structural alterations between these molecules.…”

EPR spin label study of walnut oil effects on phosphatidylcholine membranes

“…As a result, the interactions between saturated-unsaturated chains and CH-saturated chains might promote a better ordered structure. There might be some effects of the conformational properties of CH within DMPC and DPPC for the observed differences at the gel phase (Léonard et al, 2000;Endress et al, 2002). To understand the effect of WO on domain formation, two domain simulations of DPPC/16-DSA samples were performed.…”