Free Energy Landscape of Ca2+ Induced Lipid Micelle Fusion : Observation of a Dewetting Transition

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姓名

莊維夫(Wei-Fu Juang) 查詢紙本館藏

畢業系所

化學學系

論文名稱

(Free Energy Landscape of Ca2+ Induced Lipid Micelle Fusion : Observation of a Dewetting Transition)

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摘要(中)

膜融合在細胞間物質傳遞、神經傳送素釋放、以及病毒感染的過程中扮演重要的角色。其反應機制與能量變化尚未被充分了解。本篇論文採用全原子分子動態模擬法研究由鈣離子誘發兩個周圍充滿水分子的palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE)微胞自發融合的完整過程。本模擬系統類似兩個囊胞間可能開啟融合過程的小接觸帶。模擬結果顯示鈣離子有能力催化POPE微胞融合，但在類似的鈉離子模擬系統中，即使模擬時間更長，也沒有觀察到微胞融合的發生或是兩個微胞距離被拉近的情況。我們藉由energy landscape來解釋融合的反應機制。兩個微胞之間形成鈣離子-磷脂質的cluster誘發融合。由鈣離子-磷脂質的cluster所生成的prestalk state因磷脂質尾端暴露於水溶液中，所以自由能都高於接下來的stalk state 及hemifused-like state。因此，prestalk state的生成是融合過程中的速率決定步驟。本篇研究發現生成prestalk到stalk state之間的dewetting transition。Dewetting transition 決定stalk state的形成。本篇研究指出，在高水合的環境下，dewetting transition是形成stalk的關鍵步驟。

摘要(英)

Membrane fusion plays a key role in intracellular trafficking, neurotransmitter release, and viral infection. The molecular mechanism as well as energy landscape is not well understood. We have employed all-atom molecular dynamics simulations to study the entire fusion process of two hydrated 1-palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE) micelles induced by Ca2+ in a spontaneous fashion. This simulation system mimics the small contact zone between two large vesicles at which fusion may be initiated. Simulations reveal the Ca2+ is capable to catalyze the fusion of POPE micelles, whereas similar simulation with longer simulation time performed with Na+ does not observe the occurrence of fusion or even close contact of two micelles. We characterized the underlying molecular mechanism of fusion in terms of free energy landscape. The fusion is induced by the formation of inter-micelle Ca2+-lipid cluster. A prestalk state with solvent-exposed lipid tails involving in the inter-micelle Ca2+-lipid cluster has a higher free energy than the following stalk and hemifused-like states. In turn, the formation of the prestalk state is the rate-limiting step of fusion. A dewetting transition occurring in between the formation of prestalk and stalk states is observed. The formation of stalk state is determined by the dewetting transition. Our study indicates, for high hydration, the dewetting transition is the critical step in the stalk formation.

關鍵字(中)

★ 微胞融合
★ 鈣離子
★ 能量圖
★ 排水

關鍵字(英)

★ micelle fusion
★ calcium
★ energy landscape
★ dewetting

論文目次

摘要 i
Abstract ii
誌謝 iii
Table of contents iv
List of figures v
List of tables vi
Chapter 1 - Introduction 1
Chapter 2 - Computational Methods 5
Chapter 3 - Results 13
3-1 Fusion Characteristics as a Function of Time 13
3-2 Free Energy Landscape of Ca2+ Induced Micelle Fusion 22
3-3 Dewetting Transition 36
Chapter 4 - Discussion 46
Chapter 5 - Conclusions and Summary 49
References 51
Appendix A 57
Appendix B 58

參考文獻

1. Chernomordik, L. V., and M. M. Kozlov. 2005. Membrane Hemifusion: Crossing a Chasm in Two Leaps. Cell 123:375-382.
2. Jahn, R., T. Lang, and T. C. Südhof. 2003. Membrane Fusion. Cell 112:519-533.
3. Yaroslavov, A. A., A. V. Sybachin, E. Kesselman, J. Schmidt, Y. Talmon, S. A. A. Rizvi, and F. M. Menger. 2011. Liposome Fusion Rates Depend upon the Conformation of Polycation Catalysts. Journal of the American Chemical Society 133:2881-2883.
4. Shillcock, J. C., and R. Lipowsky. 2005. Tension-induced fusion of bilayer membranes and vesicles. Nat Mater 4:225-228.
5. Kasson, P., and V. S. Pande. 2007. Control of membrane fusion mechanism by lipid composition: Predictions from ensemble molecular dynamics. PLOS Comput. Biol. 3:2228-2238.
6. Portis, A., C. Newton, W. Pangborn, and D. Papahadjopoulos. 1979. Studies on the mechanism of membrane fusion: evidence for an intermembrane calcium(2+) ion-phospholipid complex, synergism with magnesium(2+) ion, and inhibition by spectrin. Biochemistry 18:780-790.
7. Schneggenburger, R., and E. Neher. 2005. Presynaptic calcium and control of vesicle fusion. Current Opinion in Neurobiology 15:266-274.
8. Ekerdt, R., and D. Papahadjopoulos. 1982. Intermembrane contact affects calcium binding to phospholipid vesicles. Proc Natl Acad Sci U S A 79:2273-2277.
9. Herbette, L., C. A. Napolitano, and R. V. McDaniel. 1984. Direct determination of the calcium profile structure for dipalmitoyllecithin multilayers using neutron diffraction. Biophys. J. 46:677-685.
10. Altenbach, C., and J. Seelig. 1984. Calcium binding to phosphatidylcholine bilayers as studied by deuterium magnetic resonance. Evidence for the formation of a calcium complex with two phospholipid molecules. Biochemistry 23:3913-3920.
11. Dluhy, R., D. G. Cameron, H. H. Mantsch, and R. Mendelsohn. 1983. Fourier transform infrared spectroscopic studies of the effect of calcium ions on phosphatidylserine. Biochemistry 22:6318-6325.
12. Tsai, H. H. G., W. X. Lai, H. D. Lin, J. B. Lee, W. F. Juang, and W. H. Tseng. 2012. Molecular dynamics simulation of cation-phospholipid clustering in phospholipid bilayers: Possible role in stalk formation during membrane fusion. Biochim. Biophys. Acta 1818:2742-2755.
13. Munih, P., M. Karplus, and G. A. Petsko. 2002. Bridged binuclear metal motif: General features through simple mg(II) and zn(II) models. Abstr. Pap. Am. Chem. Soc. 224:139-COMP.
14. Ross, M., C. Steinem, H.-J. Galla, and A. Janshoff. 2001. Visualization of Chemical and Physical Properties of Calcium-Induced Domains in DPPC/DPPS Langmuir−Blodgett Layers. Langmuir 17:2437-2445.
15. Picas, L., M. T. Montero, A. Morros, M. E. Cabañas, B. Seantier, P.-E. Milhiet, and J. Hernández-Borrell. 2009. Calcium-Induced Formation of Subdomains in Phosphatidylethanolamine−Phosphatidylglycerol Bilayers: A Combined DSC, 31P NMR, and AFM Study. J. Phys. Chem. B 113:4648-4655.
16. Schultz, Z. D., I. M. Pazos, F. K. McNeil-Watson, E. N. Lewis, and I. W. Levin. 2009. Magnesium-Induced Lipid Bilayer Microdomain Reorganizations: Implications for Membrane Fusion. J. Phys. Chem. B 113:9932-9941.
17. Schultz, Z. D., and I. W. Levin. 2008. Lipid Microdomain Formation: Characterization by Infrared Spectroscopy and Ultrasonic Velocimetry. Biophys. J. 94:3104-3114.
18. Binder, H., and O. Zschörnig. 2002. The effect of metal cations on the phase behavior and hydration characteristics of phospholipid membranes. Chem. Phys. Lipids 115:39-61.
19. Jahn, R., and H. Grubmüller. 2002. Membrane fusion. Curr. Opin. Cell Biol. 14:488-495.
20. Yang, L., and H. W. Huang. 2002. Observation of a Membrane Fusion Intermediate Structure. Science 297:1877-1879.
21. Yang, L., and H. W. Huang. 2003. A Rhombohedral Phase of Lipid Containing a Membrane Fusion Intermediate Structure. Biophys. J. 84:1808-1817.
22. Marrink, S.-J., and A. E. Mark. 2004. Molecular View of Hexagonal Phase Formation in Phospholipid Membranes. Biophys. J. 87:3894-3900.
23. Marrink, S. J., and A. E. Mark. 2003. The Mechanism of Vesicle Fusion as Revealed by Molecular Dynamics Simulations. J. Am. Chem. Soc. 125:11144-11145.
24. Kasson, P. M., N. W. Kelley, N. Singhal, M. Vrljic, A. T. Brunger, and V. S. Pande. 2006. Ensemble molecular dynamics yields submillisecond kinetics and intermediates of membrane fusion. Proc. Natl. Acad. Sci. 103:11916-11921.
25. Norizoe, Y., K. Daoulas, and M. Muller. 2010. Measuring excess free energies of self-assembled membrane structures. Faraday Discuss. 144:369-391; discussion 445-381.
26. Kozlovsky, Y., and M. M. Kozlov. 2002. Stalk model of membrane fusion: solution of energy crisis. Biophys J 82:882-895.
27. Smirnova, Y. G., S. J. Marrink, R. Lipowsky, and V. Knecht. 2010. Solvent-exposed tails as prestalk transition states for membrane fusion at low hydration. J Am Chem Soc 132:6710-6718.
28. Grafmuller, A., J. Shillcock, and R. Lipowsky. 2007. Pathway of membrane fusion with two tension-dependent energy barriers. Phys Rev Lett 98:218101.
29. Yang, Z., B. Shi, H. Lu, P. Xiu, and R. Zhou. 2011. Dewetting Transitions in the Self-Assembly of Two Amyloidogenic β-Sheets and the Importance of Matching Surfaces. J. Phys. Chem. B 115:11137-11144.
30. Krone, M. G., L. Hua, P. Soto, R. Zhou, B. J. Berne, and J.-E. Shea. 2008. Role of Water in Mediating the Assembly of Alzheimer Amyloid-β Aβ16−22 Protofilaments. J. Am. Chem. Soc. 130:11066-11072.
31. Zhou, R., X. Huang, C. J. Margulis, and B. J. Berne. 2004. Hydrophobic Collapse in Multidomain Protein Folding. Science 305:1605-1609.
32. Hua, L., X. Huang, P. Liu, R. Zhou, and B. J. Berne. 2007. Nanoscale Dewetting Transition in Protein Complex Folding. J. Phys. Chem. B 111:9069-9077.
33. Dill, K. A., and H. S. Chan. 1997. From Levinthal to pathways to funnels. Nat. Struct. Biol. 4:10-19.
34. Issa, Z. K., C. W. Manke, B. P. Jena, and J. J. Potoff. 2010. Ca2+ Bridging of Apposed Phospholipid Bilayers. J. Phys. Chem. B 114:13249-13254.
35. Knecht, V., and S.-J. Marrink. 2007. Molecular Dynamics Simulations of Lipid Vesicle Fusion in Atomic Detail. Biophys. J. 92:4254-4261.
36. Klauda, J. B., R. M. Venable, J. A. Freites, J. W. O’Connor, D. J. Tobias, C. Mondragon-Ramirez, I. Vorobyov, A. D. MacKerell, and R. W. Pastor. 2010. Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. J. Phys. Chem. B 114:7830-7843.
37. Jorgensen, W. L., J. Chandrasekhar, J. D. Madura, R. W. Impey, and M. L. Klein. 1983. Comparison of Simple Potential Functions for Simulating Liquid Water. J. Chem. Phys. 79:926-935.
38. Kale, L., R. Skeel, M. Bhandarkar, R. Brunner, A. Gursoy, N. Krawetz, J. Phillips, A. Shinozaki, K. Varadarajan, and K. Schulten. 1999. NAMD2: Greater scalability for parallel molecular dynamics. J. Comp. Phys. 151:283-312.
39. Feller, S. E., Y. H. Zhang, R. W. Pastor, and B. R. Brooks. 1995. Constant-Pressure Molecular-Dynamics Simulation - the Langevin Piston Method. J. Chem. Phys. 103:4613-4621.
40. Steinbach, P. J., and B. R. Brooks. 1994. New Spherical-Cutoff Methods for Long-Range Forces in Macromolecular Simulation. J. Comput. Chem. 15:667-683.
41. Ryckaert, J.-P., G. Ciccotti, and H. J. C. Berendsen. 1977. Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comp. Phys. 23:327-341.
42. Tieleman, D. P., D. van der Spoel, and H. J. C. Berendsen. 2000. Molecular Dynamics Simulations of Dodecylphosphocholine Micelles at Three Different Aggregate Sizes: Micellar Structure and Chain Relaxation. J. Phys. Chem. B 104:6380-6388.
43. Lee, B., and F. M. Richards. 1971. The interpretation of protein structures: Estimation of static accessibility. J. Mol. Biol. 55:379-IN374.
44. MacDonald, R. I. 1985. Membrane fusion due to dehydration by polyethylene glycol, dextran, or sucrose. Biochemistry 24:4058-4066.
45. Vernier, P. T., M. J. Ziegler, and R. Dimova. 2009. Calcium Binding and Head Group Dipole Angle in Phosphatidylserine−Phosphatidylcholine Bilayers. Langmuir 25:1020-1027.
46. Kinnunen, P. K. 1992. Fusion of lipid bilayers: a model involving mechanistic connection to HII phase forming lipids. Chem. Phys. Lipids 63:251-258.
47. Smeijers, A. F., A. J. Markvoort, K. Pieterse, and P. A. J. Hilbers. 2006. A Detailed Look at Vesicle Fusion. The Journal of Physical Chemistry B 110:13212-13219.

指導教授

蔡惠旭(Hui-Hsu Gavin Tsai)

審核日期

2012-9-26

推文