Papers by Norbert Kučerka
Neutron Scattering of Membranes
Interaction of α-tocopherol with a polyunsaturated lipid studied by MD simulations
Neutron Diffraction on Bicellar Mixtures Aligned by an In-Situ Temperature-Controllable Shear Flow Device
A recent series of papers have devised and successfully used a methodology for the detection and ... more A recent series of papers have devised and successfully used a methodology for the detection and characterization of domains in laterally heterogeneous vesicles via small-angle neutron scattering. This methodology is in seeming contradiction to similar work devised by Knoll, Haas, Stuhrmann, Fü ldner, Vogel & Sackmann [J. Appl. Cryst. (1981), 14, 191-202]. The present paper shows how these results may be reconciled.
Small-Angle Neutron Scattering Study of JV-Dodecyl-iV, iV-dimethylamine iV-Oxide Induced Solubilization of Dioleoylphosphatidylcholine Bilayers in Liposomes
Small-angle neutron scattering (SANS) curves of unilamellar dipalmitoylphosphatidylcholine (DPPC)... more Small-angle neutron scattering (SANS) curves of unilamellar dipalmitoylphosphatidylcholine (DPPC) vesicles in 1-60 mM CaCl 2 were analyzed using a strip-function model of the phospholipid bilayer. The fraction of Ca 2+ ions bound in the DPPC polar head group region was determined using Langmuir adsorption isotherm. In the gel phase, at 20 • C, the lipid bilayer thickness, d L , goes through a maximum as a function of CaCl 2 concentration (d L = 54.4 Å at ∼2.5 mM of CaCl 2 ). Simultaneously, both the area per DPPC molecule A L , and the number of water molecules n W located in the polar head group region decrease ( A L = A L(DPPC) − A L(DPPC+Ca) = 2.3 Å 2 and n = n W(DPPC) − n W(DPPC+Ca) = 0.8 mol/mol at ∼2.5 mM of CaCl 2 ). In the fluid phase, at 60 • C, the structural parameters d L , A L , and n W show evident changes with increasing Ca 2+ up to a concentration c Ca 2+ ≤ 10 mM. DPPC bilayers affected by the calcium binding are compared to unilamellar vesicles prepared by extrusion. The structural parameters of DPPC vesicles prepared in 60 mM CaCl 2 (at 20 and 60 • C) are nearly the same as those for unilamellar vesicles without Ca 2+ .
Cholesterol’s Location in Bilayers of Omega-3 PUFA Chains
α-Tocopherol is well designed to protect polyunsaturated fatty acids
The presumptive function for alpha-tocopherol (αtoc) in membranes is to protect polyunsaturated l... more The presumptive function for alpha-tocopherol (αtoc) in membranes is to protect polyunsaturated lipids against oxidation. Although the chemistry of the process is well established, the role played by molecular structure that we address here with atomistic molecular-dynamics simulations remains controversial. The simulations were run in the constant particle NPT ensemble on hydrated lipid bilayers composed of SDPC (1-stearoyl-2-docosahexaenoylphosphatidylcholine, 18:0-22:6PC) and SOPC (1-stearoyl-2-oleoylphosphatidylcholine, 18:0-18:1PC) in the presence of 20 mol % αtoc at 37°C. SDPC with SA (stearic acid) for the sn-1 chain and DHA (docosahexaenoic acid) for the sn-2 chain is representative of polyunsaturated phospholipids, while SOPC with OA (oleic acid) substituted for the sn-2 chain serves as a monounsaturated control. Solid-state (2)H nuclear magnetic resonance and neutron diffraction experiments provide validation. The simulations demonstrate that high disorder enhances the probability that DHA chains at the sn-2 position in SDPC rise up to the bilayer surface, whereby they encounter the chromanol group on αtoc molecules. This behavior is reflected in the van der Waals energy of interaction between αtoc and acyl chains, and illustrated by density maps of distribution for acyl chains around αtoc molecules that were constructed. An ability to more easily penetrate deep into the bilayer is another attribute conferred upon the chromanol group in αtoc by the high disorder possessed by DHA. By examining the trajectory of single molecules, we found that αtoc flip-flops across the SDPC bilayer on a submicrosecond timescale that is an order-of-magnitude greater than in SOPC. Our results reveal mechanisms by which the sacrificial hydroxyl group on the chromanol group can trap lipid peroxyl radicals within the interior and near the surface of a polyunsaturated membrane. At the same time, water-soluble reducing agents that regenerate αtoc can access the chromanol group when it locates at the surface.
Kučerka, N.; Nieh, M. P.; Marquardt, D.; Harroun, T. A.; Wassall, S. R.; Katsaras, J.
Soft Matter, 2014
Phosphatidylserine (PS) lipids play essential roles in biological processes, including enzyme act... more 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 62.7Å 2 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 K A 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 K A 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.
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Papers by Norbert Kučerka