Browsing by Subject "membrane architecture"

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    Interaction of α-tocopherol with a polyunsaturated lipid studied by MD simulations
    (Office of the Vice Chancellor for Research, 2013-04-05) Leng, Xiaoling; Williams, Justin A.; Marquardt, Drew; Kučerka, Norbert; Katsaras, John; Atkinson, Jeffrey; Harroun, Thad A.; Feller, Scott E.; Wassall, Stephen R.
    Polyunsaturated phospholipids are essential components of neural membranes and their effect on membrane architecture is proposed to be the molecular origin of a myriad of health benefits. A downside of polyunsaturated phospholipids is that they are highly susceptible to oxidation due to the presence of multiple double bonds. α-Tocopherol is the most biologically active component in a family of phenolic compounds that comprise vitamin E, which is the major lipid soluble antioxidant in cell membranes. To investigate whether α-tocopherol preferentially interacts with polyunsaturated phospholipids to optimize protection against oxidation, we performed MD simulations on 1-stearoyl-2-docosahexaenoylphosphatiylcholine (SDPC, 18:0-22:6PC) and 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) bilayers containing α-tocopherol. SDPC with a docosahexaenoyl sn-2 chain is polyunsaturated, while SOPC with an oleoyl sn-2 chain serves as a monounsaturated control. The simulations were run under constant pressure for 200 ns on a system that comprised 80 phospholipid molecules, 20 α-tocopherol molecules and 2165 water molecules. We discovered significant differences between the two systems. Analysis of the simulations indicates that the α-tocopherol has a strong interaction with the polyunsaturated fatty acid. The flip-flop of α-tocopherol across the bilayer is also much faster in SDPC than in SOPC. Solid state NMR, neutron scattering and complementary experiments are now underway to test the predictions from the MD simulations.
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    OxPAPC stabilizes liquid-ordered domains in biomimetic membranes
    (Elsevier BV, 2023-03) Cavazos, Andres T.; Pennington, Edward Ross; Dadoo, Sahil; Gowdy, Kymberly M.; Wassall, Stephen R.; Shaikh, Saame Raza; Physics, School of Science
    Long-chain polyunsaturated fatty acids (PUFAs) are prone to nonenzymatic oxidation in response to differing environmental stressors and endogenous cellular sources. There is increasing evidence that phospholipids containing oxidized PUFA acyl chains control the inflammatory response. However, the underlying mechanism(s) of action by which oxidized PUFAs exert their functional effects remain unclear. Herein, we tested the hypothesis that replacement of 1-palmitoyl-2-arachidonyl-phosphatidylcholine (PAPC) with oxidized 1-palmitoyl-2-arachidonyl-phosphatidylcholine (oxPAPC) regulates membrane architecture. Specifically, with solid-state 2H NMR of biomimetic membranes, we investigated how substituting oxPAPC for PAPC modulates the molecular organization of liquid-ordered (Lo) domains. 2H NMR spectra for bilayer mixtures of 1,2-dipalmitoylphosphatidylcholine-d62 (an analog of DPPC deuterated throughout sn-1 and -2 chains) and cholesterol to which PAPC or oxPAPC was added revealed that replacing PAPC with oxPAPC disrupted molecular organization, indicating that oxPAPC does not mix favorably in a tightly packed Lo phase. Furthermore, unlike PAPC, adding oxPAPC stabilized 1,2-dipalmitoylphosphatidylcholine-d6-rich/cholesterol-rich Lo domains formed in mixtures with 1,2-dioleoylphosphatidylcholine while decreasing the molecular order within 1,2-dioleoylphosphatidylcholine-rich liquid-disordered regions of the membrane. Collectively, these results suggest a mechanism in which oxPAPC stabilizes Lo domains—by disordering the surrounding liquid-disordered region. Changes in the structure, and thereby functionality, of Lo domains may underly regulation of plasma membrane-based inflammatory signaling by oxPAPC.