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研究生: 鄭景庭
Zheng, Jing-Ting
論文名稱: 利用分子動力學模擬探討多種雙親分子組成的陰陽離子液胞雙層膜在pH誘導下的相轉變行為
The pH-induced Phase Transition of Catanionic Vesicular Bilayers with Various Amphiphilic Components: A Molecular Dynamics Simulations Study
指導教授: 邱繼正
Chiu, Chi-Cheng
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2023
畢業學年度: 111
語文別: 英文
論文頁數: 67
中文關鍵詞: 分子動力學離子對雙親分子雙層膜相轉變相似水親和定律
外文關鍵詞: Molecular Dynamics, Ion Pair Amphiphile, Bilayer, Phase Transition, LMWA
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  • 摘要 i ABSTRACT ii Acknowledgment iv Table of Content v List of Tables vii List of Figures viii List of Symbols xii CHAPTER 1 INTRODUCTION 1 1.1 Liposomes as drug carriers 1 1.2 Ion Pair Amphiphile (IPA) and Catanionic Vesicle 2 1.3 pH-responsive Liposomes 3 1.4 Motivation 4 CHAPTER 2 LITERATURE REVIEW 6 2.1 Amphiphile Packing Parameters 6 2.2 pH-responsive Mechanism for pH-responsive Liposome 8 2.3 pH and Salt Effects on Ionic Amphiphile Assembly 9 2.4 Law of Matching Water Affinity (LMWA) 11 2.5 Stability of IPA Vesicles 12 CHAPTER 3 METHODOLOGY 14 3.1 Research Framework 14 3.2 IPA system with varied pH 15 3.3 Molecular Simulation Details 17 3.4 Ion Hydration and Dissociation via Umbrella Sampling 17 3.5 Hydrogen Bonding 20 3.6 Bilayer Structural & Mechanical Properties 20 3.6.1. Lateral Molecular Area 20 3.6.2. Local Membrane Thickness 21 3.6.3. Tilt Angle of Alkyl Chain 21 3.6.4. Deuterium Order Parameter 22 3.6.5. Gauche Fraction 23 3.6.6. Interdigital Value 23 3.6.7. Area Expansion Modulus 25 3.6.8. Molecular Tilt Modulus 25 3.7 Estimation of Membrane Internal Energy Change with pH 26 CHAPTER 4 RESULT AND DISCUSSION 28 4.1 Self-Assembly for Various IPA Bilayer 28 4.2 Cationic Component Variation 30 4.3 Anionic Component Variation 33 4.4 Both Variations 37 4.5 Interdigital Value (IV) 47 4.6 Estimation of Membrane Internal Energy Change with pH 50 4.7 The Length of Alkyl Chain Effect on pH Response 52 CHAPTER 5 CONCLUSIONS 56 References 59

    [1] Sercombe, L., Veerati, T., Moheimani, F., Sherry, T., Sood, A.I., and Hua, S. Advances and Challenges of Liposome Assisted Drug Delivery. Frontiers in Pharmacology 6, 286 (2015).
    [2] Ulrich, A. S. Biophysical Aspects of Using Liposomes as Delivery Vehicles. Bioscience Reports 22, 129–150 (2002).
    [3] Laverman, P. Boerman, C. O., Oyen, W. J. G., Dams, E. Th.M., Storm, G. Corstens, F. H. M. Liposomes for scintigraphic detection of infection and inflammation. Adv Drug Deliver Rev 37, 225–235 (1999).
    [4] Allen, T. M. & Cullis, P. R. Liposomal drug delivery systems: From concept to clinical applications. Adv Drug Deliver Rev 65, 36–48 (2013).
    [5] Zhu, L. & Torchilin, V. P. Stimulus-responsive nanopreparations for tumor targeting. Integr Biol 5, 96–107 (2012).
    [6] Lee, Y. & Thompson, D. H. Stimuli-responsive liposomes for drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnology 9, e1450 (2017).
    [7] Allen, T. M. & Cullis, P. R. Drug Delivery Systems: Entering the Mainstream. Science 303, 1818–1822 (2004).
    [8] Antoniou, A. I., Giofrè, S., Seneci, P., Passarella, D. & Pellegrino, S. Stimulus-responsive liposomes for biomedical applications. Drug Discov Today 26, 1794–1824 (2021).
    [9] Barenholz, Y. (Chezy). Doxil® — The first FDA-approved nano-drug: Lessons learned. J Control Release 160, 117–134 (2012).
    [10] E.W. Kaler, A.K. Murthy, B.E. Rodriguez, J.A Zasadzinski. Spontaneous vesicle formation in aqueous mixtures of single-tailed surfactants. Science, vol. 245, no.4924, pp. 1371-1374 (1989).
    [11] E. Marques, O. Regev, A. Khan, and B. Lindman, Self-organization of double-chained and pseudodouble-chained surfactants: counterion and geometry effects, Advances in colloid and interface science, vol. 100, pp. 88-104 (2003).
    [12] T. Bramer, N. Dew, and K. Edsman. Phar, aceutical application for catanionic mixtures, Journal of Pharmacy and Pharmacology, vol. 59, no. 10, pp. 1319-1334 (2007).
    [13] Soussan, E., Cassel, S., Blanzat, M. & Rico-Lattes, I. Drug Delivery by Soft Matter: Matrix and Vesicular Carriers. Angewandte Chemie Int Ed 48, 274–288 (2009).
    [14] Lioi, S. B., Wang, X., Islam, M. R., Danoff, E. J. & English, D. S. Catanionic surfactant vesicles for electrostatic molecular sequestration and separation. Phys Chem Chem Phys 11, 9315–9325 (2009).
    [15] Fukuda, H., Kawata, K., Okuda, H. & Regen, S. L. Bilayer-forming ion pair amphiphiles from single-chain surfactants. J Am Chem Soc 112, 1635–1637 (1990).
    [16] Lee, C.-H., Yang, Y.-M. & Chang, C.-H. Enhancing physical stability of positively charged catanionic vesicles in the presence of calcium chloride via cholesterol-induced fluidic bilayer characteristic. Colloid Polym Sci 292, 2519–2527 (2014).
    [17] Kuo, A.-T. & Chang, C.-H. Cholesterol-Induced Condensing and Disordering Effects on a Rigid Catanionic Bilayer: A Molecular Dynamics Study. Langmuir 30, 55–62 (2014).
    [18] Walker, S. A. & Zasadzinski, J. A. Electrostatic Control of Spontaneous Vesicle Aggregation. Langmuir 13, 5076–5081 (1997).
    [19] Kuo, A.-T., Chang, C.-H. & Shinoda, W. Molecular Dynamics Study of Catanionic Bilayers Composed of Ion Pair Amphiphile with Double-Tailed Cationic Surfactant. Langmuir 28, 8156–8164 (2012).
    [20] Felber, A. E., Dufresne, M.-H. & Leroux, J.-C. pH-sensitive vesicles, polymeric micelles, and nanospheres prepared with polycarboxylates. Adv Drug Deliver Rev 64, 979–992 (2012).
    [21] D.C. Drummond, M. Zignani, J.-C. Leroux, Current status of pH-sensitive liposomes in drug delivery, Prog. Lipid Res. 39 409–460 (2000).
    [22] S. Simões, J.N. Moreira, C. Fonseca, N. Düzgünes, M.C. Pedroso de Lima, On the formulation of pH-sensitive liposomes with long circulation times, Adv. Drug Deliv. Rev. 56 947–965 (2004).
    [23] R.R. Sawant, V.P. Torchilin, Liposomes as ‘smart’ pharmaceutical nanocarriers, Soft Matter 6 4026–4044 (2010).
    [24] Soares, D. C. F. et al. Liposomes radiolabeled with 159Gd-DTPA-BMA: Preparation, physicochemical characterization, release profile and in vitro cytotoxic evaluation. Eur J Pharm Sci 42, 462–469 (2011).
    [25] Tanford, C. The Hydrophobic Effect; Wiley-Interscience: New York, 1973.
    [26] Israelachvili, J. N., Mitchell, D. J. & Ninham, B. W. Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers. J Chem Soc Faraday Transactions 2 Mol Chem Phys 72, 1525–1568 (1976).
    [27] Nagarajan, R. Molecular Packing Parameter and Surfactant Self-Assembly: The Neglected Role of the Surfactant Tail †. Langmuir 18, 31–38 (2002).
    [28] Karanth, H. & Murthy, R. S. R. pH-Sensitive liposomes-principle and application in cancer therapy. J Pharm Pharmacol 59, 469–483 (2007).
    [29] Sawant, R. R. & Torchilin, V. P. Liposomes as ‘smart’ pharmaceutical nanocarriers. Soft Matter 6, 4026–4044 (2010).
    [30] Kang, B., Tang, H., Zhao, Z. & Song, S. Hofmeister Series: Insights of Ion Specificity from Amphiphilic Assembly and Interface Property. Acs Omega 5, 6229–6239 (2020).
    [31] Jiang, Y., Geng, T., Li, Q., Li, G. & Ju, H. Influences of temperature, pH and salinity on the surface property and self-assembly of 1:1 salt-free catanionic surfactant. J Mol Liq 199, 1–6 (2014).
    [32] Liu, C. et al. Effects of interfacial specific cations and water molarities on AOT micelle-to-vesicle transitions by chemical trapping: the specific ion-pair/hydration model. Phys Chem Chem Phys 21, 8633–8644 (2019).
    [33] Kang, B., Tang, H., Zhao, Z. & Song, S. Hofmeister Series: Insights of Ion Specificity from Amphiphilic Assembly and Interface Property. Acs Omega 5, 6229–6239 (2020).
    [34] Morris, D. F. C. In Structure And Bonding; Hemmerich, P., Jørgensen, C. K., Neilands, J. B., Nyholm, S. R. S., Reinen, D., Williams, R. J. P., Eds.; Structure and Bonding; Springer: Berlin, Heidelberg, 1969; Vol. 6; pp 157−159.
    [35] Collins, K. D. Charge Density-dependent Strength of Hydration and Biological Structure. Biophys. J. 1997, 72, 65−76.
    [36] Collins, K. D. Why Continuum Electrostatics Theories Cannot Explain Biological Structure, Polyelectrolytes or Ionic Strength Effects in Ion-protein Interactions. Biophys. Chem. 2012, 167, 43−59.
    [37] Collins, K. D. Ions from the Hofmeister Series and Osmolytes: Effects on Proteins in Solution and in the Crystallization Process. Methods 2004, 34, 300−311. Macromolecular Crystallization.
    [38] Collins, K. D. Ion Hydration: Implications for Cellular Function, Polyelectrolytes, and Protein Crystallization. Biophys. Chem. 2006, 119, 271−281.
    [39] Collins, K. D.; Neilson, G. W.; Enderby, J. E. Ions in Water: Characterizing the Forces That Control Chemical Processes and Biological Structure. Biophys. Chem. 2007, 128, 95−104
    [40] Mazzini, V. & Craig, V. S. J. Volcano Plots Emerge from a Sea of Nonaqueous Solvents: The Law of Matching Water Affinities Extends to All Solvents. Acs Central Sci 4, 1056–1064 (2018).
    [41] Šegota, S. & Težak, D. Spontaneous formation of vesicles. Adv Colloid Interfac 121, 51–75 (2006).
    [42] Hafez, I. M. & Cullis, P. R. Cholesteryl hemisuccinate exhibits pH sensitive polymorphic phase behavior. Biochimica et Biophysica Acta (BBA) - Biomembranes 1463, 107–114 (2000).
    [43] Monteiro, L. O. F. et al. Paclitaxel-Loaded pH-Sensitive Liposome: New Insights on Structural and Physicochemical Characterization. Langmuir 34, 5728–5737 (2018).
    [44] Hiemenz PC, Rajagopalan R. Principles of colloid and surfaces chemistry. New York: Marcel Dekker, Inc.; 1997.
    [45] Martínez, L., Andrade, R., Birgin, E. G. & Martínez, J. M. PACKMOL: A package for building initial configurations for molecular dynamics simulations. J. Comput. Chem. 30, 2157–2164 (2009).
    [46] Hess, B., Kutzner, C., Spoel, D. van der & Lindahl, E. GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. J Chem Theory Comput 4, 435–447 (2008).
    [47] Pronk, S. et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29, 845–854 (2013).
    [48] Lee, S. et al. CHARMM36 United Atom Chain Model for Lipids and Surfactants. J Phys Chem B 118, 547–556 (2014).
    [49] Yu, Y. & Klauda, J. B. Update of the CHARMM36 United Atom Chain Model for Hydrocarbons and Phospholipids. J Phys Chem B 124, 6797–6812 (2020).
    [50] National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 13583, Dodecylamine. Retrieved January 13, 2023.
    [51] National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 3893, Lauric Acid. Retrieved January 13, 2023.
    [52] Xinhua Wang, "2'-Propionate clarithromycin dodecyl sulfate and its preparation and pharmaceutical composition containing the same." U.S. Patent US20020037864, issued March 28, 2002.
    [53] Nosé, S. A unified formulation of the constant temperature molecular dynamics methods. J Chem Phys 81, 511–519 (1984).
    [54] Nosé, S. A molecular dynamics method for simulations in the canonical ensemble. Mol Phys 52, 255–268 (1984).
    [55] Hoover, W. G. Canonical dynamics: Equilibrium phase-space distributions. Phys Rev A 31, 1695–1697 (1985).
    [56] Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: A new molecular dynamics method. J Appl Phys 52, 7182–7190 (1981).
    [57] Darden, T., York, D. & Pedersen, L. Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems. J Chem Phys 98, 10089–10092 (1993).
    [58] Essmann, U. et al. A smooth particle mesh Ewald method. J Chem Phys 103, 8577–8593 (1995).
    [59] Hess, B., Bekker, H., Berendsen, H. J. C. & Fraaije, J. G. E. M. LINCS: A linear constraint solver for molecular simulations. J Comput Chem 18, 1463–1472 (1997).
    [60] Allen, W. J., Lemkul, J. A. & Bevan, D. R. GridMAT-MD: A grid-based membrane analysis tool for use with molecular dynamics. J. Comput. Chem. 30, 1952–1958 (2009).
    [61] H. Schindler and J. Sellig. Deuterium order parameters in relation to thermodynamic properties of phospholipid bilayer. Statistical mechanical interpretation, Biochemistry, vol 14, no. 11, pp.2283-2287 (1975).
    [62] J. seelig, Deuterium magnetic resonance: theory and application to lipid membranes, Quarterly reviews of biophysics, vol. 10, no 3, pp. 353-418 (1977)
    [63] Heller, H., Schaefer, M. & Schulten, K. Molecular dynamics simulation of a bilayer of 200 lipids in the gel and in the liquid crystal phase. J Phys Chem 97, 8343–8360 (1993).
    [64] Vermeer, L. S., De Groot, B. L., Réat, V., Milon, A. & Czaplicki, J.. Acyl chain order parameter profiles in phospholipid bilayers: computation from molecular dynamics simulations and comparison with 2H NMR experiments. European Biophysics Journal 36, 919–931 (2007).
    [65] Feller, S. E. & Pastor, R. W. Constant surface tension simulations of lipid bilayers: The sensitivity of surface areas and compressibilities. J Chem Phys 111, 1281–1287 (1999).
    [66] Anézo, C., De Vries, A. H., Höltje, H.-D., Tieleman, D. P. & Marrink, S.-J.. Methodological Issues in Lipid Bilayer Simulations. The Journal of Physical Chemistry B 107, 9424–9433 (2003).
    [67] Shinoda, W., Shinoda, K., Baba, T. & Mikami, M.. Molecular Dynamics Study of Bipolar Tetraether Lipid Membranes. Biophysical Journal 89, 3195–3202 (2005).
    [68] Khelashvili, G., Pabst, G. & Harries, D. Cholesterol Orientation and Tilt Modulus in DMPC Bilayers. J Phys Chem B 114, 7524–7534 (2010).
    [69] Khelashvili, G. & Harries, D.. How Cholesterol Tilt Modulates the Mechanical Properties of Saturated and Unsaturated Lipid Membranes. The Journal of Physical Chemistry B 117, 2411–2421 (2013).
    [70] Khelashvili, G., Kollmitzer, B., Heftberger, P., Pabst, G. & Harries, D.. Calculating the Bending Modulus for Multicomponent Lipid Membranes in Different Thermodynamic Phases. Journal of Chemical Theory and Computation 9, 3866–3871 (2013).
    [71] Radial Distribution Functions and their Role in Modeling of Mixtures Behavior.
    [72] Johnson, Q. R., Mostofian, B., Fuente Gomez, G., Smith, J. C. & Cheng, X.. Effects of carotenoids on lipid bilayers. Physical Chemistry Chemical Physics 20, 3795–3804 (2018).
    [73] Bussi, G. & Tribello, G. A. Analyzing and biasing simulations with PLUMED. Arxiv (2018) doi:10.1007/978-1-4939-9608-7_21.
    [74] Humphrey. W, Dalk A, and Schulten, K. VMD: visual molecular dynamics, Journal of molecular graphics, vol 14, no. 1, pp. 33-38 (1996).
    [75] Cantor, R. S.. The Lateral Pressure Profile in Membranes:  A Physical Mechanism of General Anesthesia. Biochemistry 36, 2339–2344 (1997).
    [76] Banavali, N. K. & Roux, B.. Free Energy Landscape of A-DNA to B-DNA Conversion in Aqueous Solution. Journal of the American Chemical Society 127, 6866–6876 (2005).
    [77] Kumar, S., Rosenberg, J. M., Bouzida, D., Swendsen, R. H. & Kollman, P. A. THE weighted histogram analysis method for free-energy calculations on biomolecules. I. The method. J. Comput. Chem. 13, 1011–1021 (1992).
    [78] Souaille, M. & Roux, B. Extension to the weighted histogram analysis method: combining umbrella sampling with free energy calculations. Comput. Phys. Commun. 135, 40–57 (2001).
    [79] A.Grossfield, “An implementation of WHAM: the Weighted Histogram Analysis Method Version 2.0.9.”
    [80] Roux, B. The calculation of the potential of mean force using computer simulations. Comput. Phys. Commun. 91, 275–282 (1995).
    [81] Guàrdia, E., Martí, J., García-Tarrés, L. & Laria, D. A molecular dynamics simulation study of hydrogen bonding in aqueous ionic solutions. J. Mol. Liq. 117, 63–67 (2005).
    [82] Luzar, A. Resolving the hydrogen bond dynamics conundrum. The J. Chem. Phys. 113, 10663–10675 (2000).

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