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

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

doi:10.3390/sym13081441

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

Journal Article · Thu Aug 05 00:00:00 EDT 2021 · Symmetry

DOI:https://doi.org/10.3390/sym13081441· OSTI ID:2471481

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University of Graz (Austria); Institut Laue-Langevin (ILL), Grenoble (France); BioTechMed Graz (Austria)
University of Virginia School of Medicine, Charlottesville, VA (United States)
University of Tennessee, Knoxville, TN (United States)
University of Tennessee, Knoxville, TN (United States); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
University of Graz (Austria); BioTechMed Graz (Austria)
Institut Laue-Langevin, Grenoble (France)

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.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: National Institutes of Health (NIH); National Science Foundation (NSF); USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 2471481

Journal Information:: Symmetry, Journal Name: Symmetry Journal Issue: 8 Vol. 13; ISSN 2073-8994

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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

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