The Molecular Structure of a Phosphatidylserine Bilayer Determined by Scattering and Molecular Dynamics Simulations

Journal Article · Wed Jan 01 04:00:00 EST 2014 · Soft Matter

DOI:https://doi.org/10.1039/c4sm00066h· OSTI ID:1133561

Pan, Jianjun ^[1]; Cheng, Xiaolin ^[2]; Monticelli, Luca ^[3]; Heberle, Frederick A ^[2]; Kucerka, Norbert ^[4]; Tieleman, D. Peter ^[5]; Katsaras, John ^[2]

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1. University of South Florida, Tampa (USF)
2. ORNL
3. Institut National de la Santé et de la Recherche Médicale (INSERM) and INTS, France
4. Atomic Energy of Canada Limited (AECL), Canadian Neutron Beam Centre (CNBC) and Comenius University,
5. University of Calgary, ALberta, Canada

Phosphatidylserine (PS) lipids play essential roles in biological processes, including enzyme activation and apoptosis. We report on the molecular structure and atomic scale interactions of a fluid bilayer composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS). A scattering density profile model, aided by molecular dynamics (MD) simulations, was developed to jointly refine different contrast small-angle neutron and X-ray scattering data, which yielded a lipid area of 62.7 A2 at 25 C. MD simulations with POPS lipid area constrained at different values were also performed using all-atom and aliphatic united-atom models. The optimal simulated bilayer was obtained using a model-free comparison approach. Examination of the simulated bilayer, which agrees best with the experimental scattering data, reveals a preferential interaction between Na+ ions and the terminal serine and phosphate moieties. Long-range inter-lipid interactions were identified, primarily between the positively charged ammonium, and the negatively charged carboxylic and phosphate oxygens. The area compressibility modulus KA of the POPS bilayer was derived by quantifying lipid area as a function of surface tension from area-constrained MD simulations. It was found that POPS bilayers possess a much larger KA than that of neutral phosphatidylcholine lipid bilayers. We propose that the unique molecular features of POPS bilayers may play an important role in certain physiological functions.

• Research Organization: Oak Ridge National Laboratory (ORNL); High Flux Isotope Reactor (HFIR); Spallation Neutron Source; Center for Structural Molecular Biology (CSMB)
• Sponsoring Organization: SC USDOE - Office of Science (SC)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 1133561
• Journal Information: Soft Matter, Journal Name: Soft Matter Journal Issue: 21 Vol. 10; ISSN 1744-683X
• Country of Publication: United States
• Language: English

Related Subjects

biomembranes
lipid bilayers
molecular dynamics simulations
neutron scattering