25-Hydroxycholesterol Effect on Membrane Structure and Mechanical Properties.

Marco M. Domingues,Nuno C. Santos,Axel Hollmann,Bárbara Gomes

doi:10.3390/ijms22052574

Abstract

Cholesterol is responsible for the plasticity of plasma membranes and is involved in physiological and pathophysiological responses. Cholesterol homeostasis is regulated by oxysterols, such as 25-hydroxycholesterol. The presence of 25-hydroxycholesterol at the membrane level has been shown to interfere with several viruses’ entry into their target cells. We used atomic force microscopy to assess the effect of 25-hydroxycholesterol on different properties of supported lipid bilayers with controlled lipid compositions. In particular, we showed that 25-hydroxycholesterol inhibits the lipid-condensing effects of cholesterol, rendering the bilayers less rigid. This study indicates that the inclusion of 25-hydroxycholesterol in plasma membranes or the conversion of part of their cholesterol content into 25-hydroxycholesterol leads to morphological alterations of the sphingomyelin (SM)-enriched domains and promotes lipid packing inhomogeneities. These changes culminate in membrane stiffness variations.

Highlights

Lipid membranes are composed of a plethora of phospholipids, sphingolipids and sterols
supported lipid bilayer (SLB) with equimolar concentrations of 1,2-dioleoyl-sn-glycero3-phosphocholine (DOPC), SM and Chol yielded differences in height between the Lo and Ld phases of 0.6 ± 0.1 nm (Figure 1B), which matches previous reports [22,23]
The lighter domains observed in the SLBs correspond to the SM and Chol-enriched Lo phase, coexisting with the darker background of the DOPC-enriched Ld phase (Figure 1A,B)

Summary

Introduction

Lipid membranes are composed of a plethora of phospholipids, sphingolipids and sterols. Lipid rafts are membrane-level molecular associations enriched in cholesterol and sphingolipids, involving van der Waals forces and hydrogen bonding [4], which are considered to take part in membrane trafficking and signaling processes [5]. Their presence in lipid mixtures is responsible for changes in membrane properties, with decreased membrane fluidity and higher ordering, creating a liquid-ordered (Lo) phase in coexistence with a liquid-disordered (Ld) phase [6,7]. When cholesterol is removed from the membrane, packing and rigidity decrease, while water permeability increases [8]

Results

Discussion

Conclusion