Geometrical Effects of Phospholipid Double Bond on the Structure and Dynamics of Membranes: A Molecular Dynamics Study

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李鴻昇(Hung-sheng Li) 查詢紙本館藏

畢業系所

化學學系

論文名稱

(Geometrical Effects of Phospholipid Double Bond on the Structure and Dynamics of Membranes: A Molecular Dynamics Study)

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摘要(中)

反式脂肪酸被發現在含有脂肪或油的食品中，特別是通過部分氫化、除臭或高溫油炸等處理過程的加工食品，並且反式脂肪酸也已被發現存在於人體脂肪組織。攝取反式脂肪酸被認為是對健康有害的危險因素，如關聯至冠狀動脈疾病和造成心臟疾病的風險等。在這項研究中，我們進行了長時間尺度的全原子分子動態模擬，探討順式單元不飽和脂質POPC(1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) 與反式單元不飽和脂質PEPC(1-palmitoyl-2-elaidoyl-sn-glycero-3-phosphocholine) 這兩種脂質膜系統，以及POPC和PEPC脂質的混合膜系統，不同雙鍵構型在結構和動態性質上造成的影響。我們從模擬中發現順式或反式雙鍵的幾何構型，可以改變鄰近雙鍵的兩個扭轉角的構型和動態，不同於碳鏈上其他飽和的扭轉角。PEPC脂質結構上相鄰反式雙鍵的兩個扭轉角，主要是採取非平面的skew-trans 構型模組和平面的cis-trans構型模組；POPC脂質結構上相鄰順式雙鍵的兩個扭轉角，卻是主要採取非平面的skew-trans和skew-gauche構型模組。然而POPC和PEPC在相鄰雙鍵的兩個扭轉角擁有相似的動態性質：比起碳鏈上其他飽和的扭轉角，第一鄰近雙鍵的扭轉角有較快的旋轉運動，相反的是第二鄰近的扭轉角卻有較慢的旋轉運動。與POPC脂質相比較，PEPC脂質擁有較佳的膜堆疊，因此導致比較小的平均頭基面積，與比較高的碳鏈秩序參數，以及比較小的擴散係數。POPC與PEPC脂質間獨特的性質差異，使得在以POPC為基質的系統內，PEPC能夠聚集形成脂質域。

摘要(英)

Trans fatty acid isomers have been identified in the foods containing fats and oils, which were particularly processed through the partial hydrogenation, deodorization or frying at high temperatures and have been found to present in human adipose tissue. The trans fatty acid isomers have also been identified to link with some harmful health effects such as coronary artery diseases and risk factors of heart attack. In this study, we performed long time-scale MD simulations using all-atom force field to investigate the structure and dynamics properties of mono-cis-unsaturated POPC(1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and mono-trans-unsaturated PEPC(1-palmitoyl-2-elaidoyl-sn-glycero-3-phosphocholine) lipids as well as the mixed systems of POPC and PEPC lipids. Our simulations found the geometry of the (cis or trans) double bond can alter the conformations and dynamics of the two torsion angles next to the double bond from those of saturated torsion angles. The two torsion angles of the PEPC lipids next to the double bond mainly adopt a non-planar skew-trans and planar cis-trans motifs; the POPC lipids mainly adopt a non-planar skew-trans and skew-gauche motifs. POPC and PEPC lipids have similar dynamical properties of the two torsion angles next to the double bond: first torsion angles have fast rotational motions and in contrast, the second torsion angles have slower rotational motions than those of saturated torsion angles. PEPC lipids have better packing than POPC lipids leading to smaller area per lipid, higher order parameter, and smaller diffusion coefficient. The distinct properties of POPC and PEPC lipids allow PEPC lipids to form domain within POPC matrix.

關鍵字(中)

★ 反式脂質
★ 雙鍵

關鍵字(英)

★ PEPC
★ trans lipid
★ double bond

論文目次

摘要 i
Abstract ii
誌謝 iii
Table of Contents v
List of Figures vi
List of Tables viiii
Chapter 1 – Introduction 1
Chapter 2 – Methods 5
Chapter 3 – Results 8
3.1 Area per Lipid and Membrane Thickness 8
3.2 Order Parameters of Acyl Chains 11
3.3 Conformation of Acyl Chains 14
3.4 Conformation Lifetimes of the Acyl Chains 25
3.5 Dynamics of Torsion Angles 33
3.6 Lateral Diffusion Coefficient 35
3.7 PEPC Domain Formation of 3O1E Mixed System 38
Chapter 4 – Discussion 45
Chapter 5 – Conclusion and Summary 49
References 50
Appendix A 54
Appendix B 55
Appendix C 57
Appendix D 58
Appendix E 59
Appendix F 61

參考文獻

1. Tattrie, N.H., J.R. Bennett, and R. Cyr, Maximum and minimum values for lecithin classes from various biological sources. Canadian Journal of Biochemistry, 1968. 46(8): p. 819-824.
2. Fox, B.G., K.S. Lyle, and C.E. Rogge, Reactions of the Diiron Enzyme Stearoyl-Acyl Carrier Protein Desaturase. Accounts of Chemical Research, 2004. 37(7): p. 421-429.
3. Ferreri, C. and C. Chatgilialoglu, Geometrical trans lipid isomers: a new target for lipidomics. Chembiochem, 2005. 6(10): p. 1722-34.
4. Okuyama, H., et al., The cis/trans isomerization of the double bond of a fatty acid as a strategy for adaptation to changes in ambient temperature in the psychrophilic bacterium, Vibrio sp. strain ABE-1. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1991. 1084(1): p. 13-20.
5. Kieft, T.L., D.B. Ringelberg, and D.C. White, Changes in Ester-Linked Phospholipid Fatty Acid Profiles of Subsurface Bacteria during Starvation and Desiccation in a Porous Medium. Applied and Environmental Microbiology, 1994. 60(9): p. 3292-3299.
6. Halverson, L.J. and M.K. Firestone, Differential Effects of Permeating and Nonpermeating Solutes on the Fatty Acid Composition of Pseudomonas putida. Applied and Environmental Microbiology, 2000. 66(6): p. 2414-2421.
7. Heipieper, H.J., R. Diefenbach, and H. Keweloh, Conversion of cis unsaturated fatty acids to trans, a possible mechanism for the protection of phenol-degrading Pseudomonas putida P8 from substrate toxicity. Applied and Environmental Microbiology, 1992. 58(6): p. 1847-1852.
8. Romero, A., C. Cuesta, and F.J. Sánchez-Muniz, Trans fatty acid production in deep fat frying of frozen foods with different oils and frying modalities. Nutrition Research, 2000. 20(4): p. 599-608.
9. Wolff, R.L. and B. Entressangles, Steady-state fluorescence polarization study of structurally defined phospholipids from liver mitochondria of rats fed elaidic acid. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1994. 1211(2): p. 198-206.
10. B Woldseth, K.R.B.O.C., Monounsaturated trans fatty acids, elaidic acid and trans-vaccenic acid, metabolism and incorporation in phospholipid molecular species in hepatocytes. Scandinavian Journal of Clinical & Laboratory Investigation, 1998. 58(8): p. 635-645.
11. Seelig, J. and N. Waespe-Sarcevic, Molecular order in cis and trans unsaturated phospholipid bilayers. Biochemistry, 1978. 17(16): p. 3310-3315.
12. Soni, S.P., et al., Effect of trans unsaturation on molecular organization in a phospholipid membrane. Biochemistry, 2009. 48(46): p. 11097-107.
13. Murzyn, K., et al., Effects of phospholipid unsaturation on the membrane/water interface: a molecular simulation study. Biophys J, 2001. 81(1): p. 170-83.
14. Rog, T., et al., Effects of phospholipid unsaturation on the bilayer nonpolar region: a molecular simulation study. J Lipid Res, 2004. 45(2): p. 326-36.
15. Janosi, L. and A. Gorfe, Importance of the sphingosine base double-bond geometry for the structural and thermodynamic properties of sphingomyelin bilayers. Biophys J, 2010. 99(9): p. 2957-66.
16. Niu, S.L., D.C. Mitchell, and B.J. Litman, Trans fatty acid derived phospholipids show increased membrane cholesterol and reduced receptor activation as compared to their cis analogs. Biochemistry, 2005. 44(11): p. 4458-65.
17. Roach, C., et al., Comparison of cis and trans fatty acid containing phosphatidylcholines on membrane properties. Biochemistry, 2004. 43(20): p. 6344-51.
18. Mathai, J.C., et al., Structural determinants of water permeability through the lipid membrane. J Gen Physiol, 2008. 131(1): p. 69-76.
19. Bjorkbom, A., B. Ramstedt, and J.P. Slotte, Phosphatidylcholine and sphingomyelin containing an elaidoyl fatty acid can form cholesterol-rich lateral domains in bilayer membranes. Biochim Biophys Acta, 2007. 1768(7): p. 1839-47.
20. Wiberg, K.B. and E. Martin, Barriers to rotation adjacent to double bonds. Journal of the American Chemical Society, 1985. 107(18): p. 5035-5041.
21. Kondo, S., E. Hirota, and Y. Morino, Microwave spectrum and rotational isomerism in butene-1. Journal of Molecular Spectroscopy, 1968. 28(4): p. 471-489.
22. Kaneko, F., J. Yano, and K. Sato, Diversity in the fatty-acid conformation and chain packing of cis-unsaturated lipids. Curr Opin Struct Biol, 1998. 8(4): p. 417-25.
23. Di, L. and D.M. Small, Physical behavior of the mixed chain diacylglycerol, 1-stearoyl-2-oleoyl-sn-glycerol: difficulties in chain packing produced marked polymorphism. J Lipid Res, 1993. 34(9): p. 1611-23.
24. Plesnar, E., W.K. Subczynski, and M. Pasenkiewicz-Gierula, Saturation with cholesterol increases vertical order and smoothes the surface of the phosphatidylcholine bilayer: a molecular simulation study. Biochim Biophys Acta, 2012. 1818(3): p. 520-9.
25. Martinez-Seara, H., et al., Influence of cis double-bond parametrization on lipid membrane properties: how seemingly insignificant details in force-field change even qualitative trends. J Chem Phys, 2008. 129(10): p. 105103.
26. Bachar, M., et al., Molecular dynamics simulation of a polyunsaturated lipid bilayer susceptible to lipid peroxidation. Journal of Physical Chemistry B, 2004. 108(22): p. 7170-7179.
27. Ueno, S., et al., Structure and polymorphic transformations in elaidic acid (trans-ω9-octadecenoic acid). Chemistry and Physics of Lipids, 1994. 72(1): p. 27-34.
28. Low, J.N., C. Scrimgeour, and P. Horton, Elaidic acid (trans-9-octadecenoic acid). Acta Crystallographica Section E Structure Reports Online, 2005. 61(11): p. o3730-o3732.
29. Jo, S., et al., CHARMM-GUI: A web-based graphical user interface for CHARMM. Journal of Computational Chemistry, 2008. 29(11): p. 1859-1865.
30. Kale, L., et al., NAMD2: Greater scalability for parallel molecular dynamics. Journal of Computational Physics, 1999. 151(1): p. 283-312.
31. Klauda, J.B., et al., Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. The Journal of Physical Chemistry B, 2010. 114(23): p. 7830-7843.
32. Jorgensen, W.L., et al., Comparison of Simple Potential Functions for Simulating Liquid Water. Journal of Chemical Physics, 1983. 79(2): p. 926-935.
33. Ryckaert, J.-P., G. Ciccotti, and H.J.C. Berendsen, Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. Journal of Computational Physics, 1977. 23(3): p. 327-341.
34. Feller, S.E., et al., Constant-Pressure Molecular-Dynamics Simulation - the Langevin Piston Method. Journal of Chemical Physics, 1995. 103(11): p. 4613-4621.
35. Steinbach, P.J. and B.R. Brooks, New Spherical-Cutoff Methods for Long-Range Forces in Macromolecular Simulation. Journal of Computational Chemistry, 1994. 15(7): p. 667-683.
36. Shinoda, W. and S. Okazaki, A Voronoi analysis of lipid area fluctuation in a bilayer. Journal of Chemical Physics, 1998. 109(4): p. 1517-1521.
37. Allen, W.J., J.A. Lemkul, and D.R. Bevan, GridMAT-MD: A Grid-Based Membrane Analysis Tool for Use With Molecular Dynamics. Journal of Computational Chemistry, 2009. 30(12): p. 1952-1958.
38. Smaby, J.M., et al., Phosphatidylcholine acyl unsaturation modulates the decrease in interfacial elasticity induced by cholesterol. Biophysical journal, 1997. 73(3): p. 1492-1505.
39. Pabst, G., et al., Structural information from multilamellar liposomes at full hydration: Full q-range fitting with high quality x-ray data. Physical Review E, 2000. 62(3): p. 4000-4009.
40. Kučerka, N., S. Tristram-Nagle, and J. Nagle, Structure of Fully Hydrated Fluid Phase Lipid Bilayers with Monounsaturated Chains. The Journal of Membrane Biology, 2006. 208(3): p. 193-202.
41. Seelig, A. and J. Seelig, Effect of a single cis double bond on the structure of a phospholipid bilayer. Biochemistry, 1977. 16(1): p. 45-50.
42. Perly, B., I.C.P. Smith, and H.C. Jarrell, Effects of the replacement of a double bond by a cyclopropane ring in phosphatidylethanolamines: a deuterium NMR study of phase transitions and molecular organization. Biochemistry, 1985. 24(4): p. 1055-1063.
43. Poger, D. and A.E. Mark, On the Validation of Molecular Dynamics Simulations of Saturated and cis-Monounsaturated Phosphatidylcholine Lipid Bilayers: A Comparison with Experiment. Journal of Chemical Theory and Computation, 2010. 6(1): p. 325-336.
44. Venable, R.M., et al., Molecular dynamics simulations of a lipid bilayer and of hexadecane: an investigation of membrane fluidity. Science, 1993. 262(5131): p. 223-6.
45. Boyd, R.H., et al., Conformational Dynamics in Bulk Polyethylene - a Molecular-Dynamics Simulation Study. Journal of Chemical Physics, 1994. 101(1): p. 788-797.
46. Vaz, W.L.C., R.M. Clegg, and D. Hallmann, Translational diffusion of lipids in liquid crystalline phase phosphatidylcholine multibilayers. A comparison of experiment with theory. Biochemistry, 1985. 24(3): p. 781-786.
47. Li, S., et al., Identification and characterization of kink motifs in 1-palmitoyl-2-oleoyl- phosphatidylcholines: a molecular mechanics study. Biophys J, 1994. 66(6): p. 2005-18.

指導教授

蔡惠旭(Hui-Hsu Gavin Tsai)

審核日期

2014-7-18

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