The Structure of Cholesterol in Lipid Rafts

TL;DR

This study combines simulations and neutron diffraction to investigate cholesterol organization in lipid rafts, revealing ordered cholesterol domains and pairing consistent with the umbrella model.

Contribution

It provides new insights into the nanoscale structure and ordering of cholesterol in lipid rafts using combined experimental and computational methods.

Findings

Identification of small, ordered cholesterol domains in membranes

Observation of strongly bound cholesterol pairs in the liquid-disordered phase

Detection of Bragg peaks indicating ordered cholesterol structures

Abstract

Rafts, or functional domains, are transient nano- or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking and lipid/protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short-lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules we observe raft-like structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raft-like structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.