Global small-angle scattering data analysis of inverted hexagonal phases

Abstract

A global analysis model has been developed for randomly oriented, fully hydrated, inverted hexagonal (HII) phases formed by many amphiphiles in aqueous solution, including membrane lipids. The model is based on a structure factor for hexagonally packed rods and a compositional model for the scattering length density, enabling also the analysis of positionally weakly correlated HII phases. Bayesian probability theory was used for optimization of the adjustable parameters, which allows parameter correlations to be retrieved in much more detail than standard analysis techniques and thereby enables a realistic error analysis. The model was applied to different phosphatidylethanolamines, including previously unreported HII data for diC14:0 and diC16:1 phosphatidylethanolamine. The extracted structural features include intrinsic lipid curvature, hydrocarbon chain length and area per lipid at the position of the neutral plane.

Intrinsic Lipid Curvatures of Mammalian Plasma Membrane Outer Leaflet Lipids and Ceramides

“…(3) essentially boils down to finding the neutral plane of a given lipid mixture forming the H II phase. Analogously to our previous reports [17,12] and in line with MD simulations [33], we assume that R 0 coincides with the position of the lipid backbone. Previously, we also demonstrated how to derive C 0 from a global SAXS data analysis of single lipid species forming a H II phase [12].…”

“…The global SAXS analysis of H II -forming lipid mixtures with DOPE as host developed here advances the determination of intrinsic lipid curvatures of membrane lipids, which normally do not form H II phases. In particular, we extended a previously reported combined compositional data modelling/Bayesian statistical analysis [12] with shape-based packing arguments to address potential non-linear mixing contributions.…”

“…In order to address these issues, we advance a previously reported compositional analysis technique for H II phases [12] to lipid mixtures including nonlinear mixing contributions based on lipid shape. The model is validated against all-atom molecular dynamics simulations and then applied to PCs with saturated, unsaturated and branched hydrocarbons, PSM, as well as C2:0, C6:0, C16:0 and C24:0 ceramide.…”

“…That is, its value depends on the lipids' steric size, as well as on the attractive and repulsive interactions along vatures of lipids that do not form inverted hexagonal phases (H II ) in aqueous solution. Inverted hexagonal mesophases are convenient for the determination of C 0 using structure sensitive techniques, such as small-angle X-ray scattering (SAXS) [12]. In order to derive C 0 for bilayer-forming lipids, these lipids ('guest') are commonly added to H II -forming templates ('host') assuming linear mixing [13,14,15,16,17,18].…”

Increasing complexity in small-angle X-ray and neutron scattering experiments: from biological membrane mimics to live cells

“…For computational reasons it has been proven useful to parse the lipid molecule into different slabs, where R 0 is located in the center of the lipid backbone slab. 65 Beside the headgroup size, C 0 is closely connected to the hydrocarbon chain composition (length and number of double bonds), which causes some disaturated phosphatidylethanolamines such as DMPE (dimyristoyl-phospatidylethanolamine) to have their L a -H II phase transition, T H , at physiologially unrealistic temperatures. Experiments with H II phases are frequently performed with additional hydrophobic agents such as alkanes 61,66 or alkenes.…”