Structure and Interdigitation of Chain-Asymmetric Phosphatidylcholines and Milk Sphingomyelin in the Fluid Phase.

Lionel Porcar,Georg Pabst,Moritz P. K. Frewein,Frederick A. Heberle,Haden L. Scott,Milka Doktorova,Enrico F. Semeraro

doi:10.3390/sym13081441

Abstract

We addressed the frequent occurrence of mixed-chain lipids in biological membranes and their impact on membrane structure by studying several chain-asymmetric phosphatidylcholines and the highly asymmetric milk sphingomyelin. Specifically, we report trans-membrane structures of the corresponding fluid lamellar phases using small-angle X-ray and neutron scattering, which were jointly analyzed in terms of a membrane composition-specific model, including a headgroup hydration shell. Focusing on terminal methyl groups at the bilayer center, we found a linear relation between hydrocarbon chain length mismatch and the methyl-overlap for phosphatidylcholines, and a non-negligible impact of the glycerol backbone-tilting, letting the sn1-chain penetrate deeper into the opposing leaflet by half a CH2 group. That is, penetration-depth differences due to the ester-linked hydrocarbons at the glycerol backbone, previously reported for gel phase structures, also extend to the more relevant physiological fluid phase, but are significantly reduced. Moreover, milk sphingomyelin was found to follow the same linear relationship suggesting a similar tilt of the sphingosine backbone. Complementarily performed molecular dynamics simulations revealed that there is always a part of the lipid tails bending back, even if there is a high interdigitation with the opposing chains. The extent of this back-bending was similar to that in chain symmetric bilayers. For both cases of adaptation to chain length mismatch, chain-asymmetry has a large impact on hydrocarbon chain ordering, inducing disorder in the longer of the two hydrocarbons.

Highlights

We consecutively focused on the fluid structures of SMPC, myristoyl stearoyl PC (MSPC) and palmitoyl myristol PC (PMPC) and included monounsaturated palmitoyl oleoyl PC (POPC), stearoyl oleoyl PC (SOPC) and milk sphingomyelin (MSM), which is a natural lipid extract with high chain length asymmetry
The scattering density profile (SDP) model simultaneously accounts for small-angle neutron and the X-ray data (SANS/SAXS) of lipid bilayers enabling a unique combination of the different contrasts offered by the two techniques
For fully saturated PCs, we observed no significant effects on the overall bilayer structure resulting from the chain asymmetry, except for the overlap of their terminal methyl groups in the membrane center

Summary

Introduction

As the main structural constituents of biological membranes, glycerophospholipids and sphingolipids occur in a large variety of species, differing in their hydrophilic heads, hydrophobic tails and backbone structure. A considerable fraction of the most abundant double-chained membrane lipids exhibit distinct compositional differences of their hydrocarbons [1,2]. Combinations of a saturated and an unsaturated chain are very common for glycerophospholipids and are widely used in membrane mimics. Saturated phospholipids with mixed chain lengths are much less abundant and less frequently studied. Large chain length asymmetries including long, saturated chains are, frequent in sphingolipids, such as, e.g., sphingomyelin. Sphingomyelin contains a sphingosine backbone of 18 carbons and an acyl chain, which can largely vary in length. Further hydrocarbon chain interdigitation has been implied in the transleaflet coupling of asymmetric lipid bilayers [5,6,7]

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Results

Conclusion