High-resolution structure of coexisting nanoscopic and microscopic lipid domains

TL;DR

This study improves a scattering data analysis model to reveal detailed structural and compositional differences between nanoscopic and microscopic lipid domains in vesicles, highlighting cholesterol's distinct localization in nanodomains.

Contribution

The paper introduces an enhanced model for analyzing in situ scattering data, capable of characterizing nanoscopic lipid domains and cholesterol distribution within them.

Findings

Cholesterol tends to localize toward the bilayer center in nanoscopic domains.

The model successfully fits data for both micron-sized and nanoscopic domains.

Structural details like domain thickness and lipid area are quantitatively retrieved.

Abstract

We advanced a previously reported model for the \textit{in situ} scattering data analysis of coexisting lipid domains in free-floating multilamellar vesicles. Based on the scattering density profile of the individual domains we considered in particular modifications due to positionally anticorrelated domains or the presence of cholesterol. The latter aspect can be easily extended to any other lipophilic molecule. This allowed us to retrieve elastic and structural details (bending fluctuations, domain thickness, area per lipid) of coexisting liquid-ordered/liquid-disordered domains, including the partitioning of cholesterol from small-angle x-ray scattering experiments. Moreover, the model also successfully fitted data of multilamellar vesicles exhibiting nanoscopic domains, which displayed unlike coexisting micron-sized domains no clear signal for two lamellar lattices. Our results indicate a previously not observed translation of cholesterol toward the bilayer center of nanoscopic liquid-ordered domains.