Binding and dynamics of melatonin at the interface of phosphatidylcholine-cholesterol membranes


Autoři: Huixia Lu aff001;  Jordi Martí aff001
Působiště autorů: Department of Physics, Technical University of Catalonia-Barcelona Tech. Barcelona, Catalonia, Spain aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224624

Souhrn

The characterization of interactions between melatonin, one main ingredient of medicines regulating sleeping rhythms, and basic components of cellular plasma membranes (phospholipids, cholesterol, metal ions and water) is very important to elucidate the main mechanisms for the introduction of melatonin into cells and also to identify its local structure and microscopic dynamics. Molecular dynamics simulations of melatonin inside mixtures of dimyristoylphosphatidylcholine and cholesterol in NaCl solution at physiological concentration have been performed at 303.15 K to systematically explore melatonin-cholesterol, melatonin-lipid and melatonin-water interactions. Properties such as the area per lipid and thickness of the membrane as well as selected radial distribution functions, binding free energies, angular distributions, atomic spectral densities and translational diffusion of melatonin are reported. The presence of cholesterol significantly affects the behavior of melatonin, which is mainly buried into the interfaces of membranes. Introducing cholesterol into the system helps melatonin change from folded to extended configurations more easily. Our results suggest that there exists a competition between the binding of melatonin to phospholipids and to cholesterol by means of hydrogen-bonds. Spectral densities of melatonin reported in this work, in overall good agreement with experimental data, revealed the participation of each atom of melatonin to its complete spectrum. Melatonin self-diffusion coefficients are of the order of 10−7 cm2/s and they significantly increase when cholesterol is addeed to the membrane.

Klíčová slova:

Cell membranes – Cholesterol – Infrared spectroscopy – Lipids – Melatonin – Vibration – Membrane characteristics – Dihedral angles


Zdroje

1. Mouritsen OG. Life-As a Matter of Fat. Springer; 2005.

2. Rog T, Pasenkiewicz-Gierula M, Vattulainen I, Karttunen M. Ordering effects of cholesterol and its analogues. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2009;1788(1):97–121. doi: 10.1016/j.bbamem.2008.08.022

3. Martinez-Seara H, Rog T, Karttunen M, Vattulainen I, Reigada R. Cholesterol induces specific spatial and orientational order in cholesterol/phospholipid membranes. PloS one. 2010;5(6), e11162. doi: 10.1371/journal.pone.0011162 20567600

4. Nussinov R, Tsai CJ, Jang H. Oncogenic Ras isoforms signaling specificity at the membrane. Cancer research. 2018;78(3):593–602. doi: 10.1158/0008-5472.CAN-17-2727 29273632

5. Brzezinski A. Melatonin in humans. New England journal of medicine. 1997;336(3):186–195. doi: 10.1056/NEJM199701163360306 8988899

6. Pandi-Perumal SR, Srinivasan V, Maestroni G, Cardinali D, Poeggeler B, Hardeland R. Melatonin. The FEBS journal. 2006;273(13):2813–2838. doi: 10.1111/j.1742-4658.2006.05322.x 16817850

7. Marrink SJ, Corradi V, Souza PCT, Ingolfsson HI, Tieleman DP, Sansom MSP. Computational modeling of realistic cell membranes. Chemical reviews. 2019; 119(9):6184–6226. doi: 10.1021/acs.chemrev.8b00460 30623647

8. Needham D, McIntosh T, Evans E. Thermomechanical and transition properties of dimyristoylphosphatidylcholine/cholesterol bilayers. Biochemistry. 1988;27(13):4668–4673. doi: 10.1021/bi00413a013 3167010

9. Johnson SJ, Bayerl TM, McDermott DC, Adam GW, Rennie AR, Thomas RK, et al. Structure of an adsorbed dimyristoylphosphatidylcholine bilayer measured with specular reflection of neutrons. Biophysical journal. 1991;59(2):289–294. doi: 10.1016/S0006-3495(91)82222-6 2009353

10. Smondyrev AM, Berkowitz ML. Molecular dynamics simulation of the structure of dimyristoylphosphatidylcholine bilayers with cholesterol, ergosterol, and lanosterol. Biophysical journal. 2001;80(4):1649–1658. doi: 10.1016/S0006-3495(01)76137-1 11259280

11. Drolle E, Kučerka N, Hoopes M, Choi Y, Katsaras J, Karttunen M, et al. Effect of melatonin and cholesterol on the structure of DOPC and DPPC membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2013;1828(9):2247–2254. doi: 10.1016/j.bbamem.2013.05.015

12. Choi Y, Attwood SJ, Hoopes MI, Drolle E, Karttunen M, Leonenko Z. Melatonin directly interacts with cholesterol and alleviates cholesterol effects in dipalmitoylphosphatidylcholine monolayers. Soft Matter. 2014;10(1):206–213. doi: 10.1039/c3sm52064a 24651707

13. Mousavi SS, Shohrati M, Vahedi E, Abdollahpour-Alitappeh M, Panahi Y. Effect of melatonin administration on sleep quality in sulfur mustard exposed patients with sleep disorders. Iranian Journal of Pharmaceutical Research. 2018;17:136. 29796038

14. Savoca A, Manca D. Physiologically-based pharmacokinetic simulations in pharmacotherapy: selection of the optimal administration route for exogenous melatonin. ADMET and DMPK. 2019;7(1):44–59. doi: 10.5599/admet.625

15. Kostoglou-Athanassiou I. Therapeutic applications of melatonin. Therapeutic advances in endocrinology and metabolism. 2013;4(1):13–24. doi: 10.1177/2042018813476084 23515203

16. Slominski AT, Zmijewski MA, Semak I, Kim TK, Janjetovic Z, Slominski RM, et al. Melatonin, mitochondria, and the skin. Cellular and Molecular Life Sciences. 2017;74(21):3913–3925. doi: 10.1007/s00018-017-2617-7 28803347

17. Slominski AT, Hardeland R, Zmijewski MA, Slominski RM, Reiter RJ, Paus R. Melatonin: a cutaneous perspective on its production, metabolism, and functions. Journal of Investigative Dermatology. 2018;138(3):490–499. doi: 10.1016/j.jid.2017.10.025 29428440

18. Maestroni GJ, Sulli A, Pizzorni C, Villaggio B, Cutolo M. Melatonin in rheumatoid arthritis. Annals of the New York Academy of Sciences. 2002;966(1):271–275. doi: 10.1111/j.1749-6632.2002.tb04226.x 12114283

19. Forrest CM, Mackay GM, Stoy N, Stone TW, Darlington LG. Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin. British journal of clinical pharmacology. 2007;64(4):517–526. doi: 10.1111/j.1365-2125.2007.02911.x 17506781

20. Bang J, Chang HW, Jung HR, Cho CH, Hur JA, Lee SI, et al. Melatonin attenuates clock gene Cryptochrome1, which may aggravates mouse anti-type II collagen antibody-induced arthritis. Rheumatology international. 2012;32(2):379–385. doi: 10.1007/s00296-010-1641-9 21113809

21. Huang CC, Chiou CH, Liu SC, Hu SL, Su CM, Tsai CH, et al. Melatonin attenuates TNF-α and IL-1β expression in synovial fibroblasts and diminishes cartilage degradation: implications for the treatment of rheumatoid arthritis. Journal of pineal research. 2019; p. e12560. doi: 10.1111/jpi.12560 30648758

22. Hussain SAR. Effect of melatonin on cholesterol absorption in rats. Journal of pineal research. 2007;42(3):267–271. doi: 10.1111/j.1600-079X.2006.00415.x 17349025

23. Wang M, Duan S, Zhou Z, Chen S, Wang D. Foliar spraying of melatonin confers cadmium tolerance in Nicotiana tabacum L. Ecotoxicology and environmental safety. 2019;170:68–76. doi: 10.1016/j.ecoenv.2018.11.127 30529622

24. Marti J, Lu H. Molecular dynamics of dipalmitoylphosphatidylcholine biomembranes in ionic solution: adsorption of the precursor neurotransmitter tryptophan. Procedia Computer Science. 2017;108:1242–1250. doi: 10.1016/j.procs.2017.05.141

25. Lu H, Martí J. Effects of cholesterol on the binding of the precursor neurotransmitter tryptophan to zwitterionic membranes. The Journal of chemical physics. 2018;149(16):164906. doi: 10.1063/1.5029430 30384712

26. Lu H, Marti J. Binding free energies of small-molecules in phospholipid membranes: Aminoacids, serotonin and melatonin. Chemical Physics Letters. 2018;712:190–195. doi: 10.1016/j.cplett.2018.10.006

27. Lopez CF, Nielsen SO, Klein ML, Moore PB. Hydrogen bonding structure and dynamics of water at the dimyristoylphosphatidylcholine lipid bilayer surface from a molecular dynamics simulation. The Journal of Physical Chemistry B. 2004;108(21):6603–6610. doi: 10.1021/jp037618q

28. Yang J, Calero C, Martí J. Diffusion and spectroscopy of water and lipids in fully hydrated dimyristoylphosphatidylcholine bilayer membranes. J Chem Phys. 2014;140(10):104901. doi: 10.1063/1.4867385 24628199

29. Yang J, Martí J, Calero C. Pair interactions among ternary DPPC/POPC/cholesterol mixtures in liquid-ordered and liquid-disordered phases. Soft Matter. 2016;12(20):4557–4561. doi: 10.1039/c6sm00345a 27103534

30. Chen W, Duša F, Witos J, Ruokonen S-K, Wiedmer SK. Determination of the main phase transition temperature of phospholipids by nanoplasmonic sensing. Scientific reports. 2018; 8(1):14815. doi: 10.1038/s41598-018-33107-5 30287903

31. Jo S, Kim T, Iyer VG, Im W. CHARMM-GUI: A Web-Based Graphical User Interface for CHARMM. J Comput Chem. 2008;29(11):1859–1865. doi: 10.1002/jcc.20945 18351591

32. Jo S, Lim JB, Klauda JB, Im W. CHARMM-GUI Membrane Builder for Mixed Bilayers and Its Application to Yeast Membranes. Biophys J. 2009;97(1):50–58. doi: 10.1016/j.bpj.2009.04.013 19580743

33. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of Simple Potential Functions for Simulating Liquid Water. J Chem Phys. 1983;79(2):926–935. doi: 10.1063/1.445869

34. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, et al. Scalable Molecular Dynamics with NAMD. J Comput Chem. 2005;26(16):1781–1802. doi: 10.1002/jcc.20289 16222654

35. Klauda JB, Venable RM, Freites JA, O’Connor JW, Tobias DJ, Mondragon-Ramirez C, et al. Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. J Phys Chem B. 2010;114(23):7830–7843. doi: 10.1021/jp101759q 20496934

36. Lim JB, Rogaski B, Klauda JB. Update of the Cholesterol Force Field Parameters in CHARMM. J Phys Chem B. 2012;116(1):203–210. doi: 10.1021/jp207925m 22136112

37. Lemkul JA, Huang J, Roux B, MacKerell AD Jr. An empirical polarizable force field based on the classical drude oscillator model: development history and recent applications. Chemical reviews. 2016;116(9):4983–5013. doi: 10.1021/acs.chemrev.5b00505 26815602

38. Huang J, Rauscher S, Nawrocki G, Ran T, Feig M, de Groot BL, et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nature methods. 2017;14(1):71. doi: 10.1038/nmeth.4067 27819658

39. McMullen TP, Lewis RN, McElhaney RN. Cholesterol–phospholipid interactions, the liquid-ordered phase and lipid rafts in model and biological membranes. Current opinion in colloid & interface science. 2004;8(6):459–468. doi: 10.1016/j.cocis.2004.01.007

40. Berendsen HJ, Postma Jv, van Gunsteren WF, DiNola A, Haak J. Molecular dynamics with coupling to an external bath. J Chem Phys. 1984;81(8):3684–3690. doi: 10.1063/1.448118

41. Martyna GJ, Tobias DJ, Klein ML. Constant pressure molecular dynamics algorithms. The Journal of Chemical Physics. 1994;101(5):4177–4189. doi: 10.1063/1.467468

42. Feller SE, Zhang Y, Pastor RW, Brooks BR. Constant Pressure Molecular Dynamics Simulation: The Langevin Piston Method. J Chem Phys. 1995;103(11):4613–4621. doi: 10.1063/1.470648

43. Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG. A Smooth Particle Mesh Ewald Method. J Chem Phys. 1995;103(19):8577–8593. doi: 10.1063/1.470117

44. Stockton GW, Smith IC. A deuterium nuclear magnetic resonance study of the condensing effect of cholesterol on egg phosphatidylcholine bilayer membranes. I. Perdeuterated fatty acid probes. Chem Phys Lipids. 1976;17(2-3):251–263. doi: 10.1016/0009-3084(76)90070-0 1033045

45. Hofsäß C, Lindahl E, Edholm O. Molecular dynamics simulations of phospholipid bilayers with cholesterol. Biophys J. 2003;84(4):2192–2206. doi: 10.1016/S0006-3495(03)75025-5 12668428

46. Yeagle PL. The membranes of cells. Academic Press; 2016.

47. Berger O, Edholm O, Jähnig F. Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J. 1997;72(5):2002–2013. doi: 10.1016/S0006-3495(97)78845-3 9129804

48. Ganesan N, Bauer BA, Lucas TR, Patel S, Taufer M. Structural, dynamic, and electrostatic properties of fully hydrated DMPC bilayers from molecular dynamics simulations accelerated with graphical processing units (GPUs). Journal of computational chemistry. 2011;32(14):2958–2973. doi: 10.1002/jcc.21871 21793003

49. Trouard TP, Nevzorov AA, Alam TM, Job C, Zajicek J, Brown MF. Influence of cholesterol on dynamics of dimyristoylphosphatidylcholine bilayers as studied by deuterium NMR relaxation. J Chem Phys. 1999;110(17):8802–8818. doi: 10.1063/1.478787

50. Petrache HI, Dodd SW, Brown MF. Area per lipid and acyl length distributions in fluid phosphatidylcholines determined by 2 H NMR spectroscopy. Biophys J. 2000;79(6):3172–3192. doi: 10.1016/S0006-3495(00)76551-9 11106622

51. Pandey PR, Roy S. Headgroup mediated water insertion into the DPPC bilayer: a molecular dynamics study. J Phys Chem B. 2011;115(12):3155–3163. doi: 10.1021/jp1090203 21384811

52. Kučerka N, Nieh MP, Katsaras J. Fluid phase lipid areas and bilayer thicknesses of commonly used phosphatidylcholines as a function of temperature. BBA-Biomembranes. 2011;1808(11):2761–2771. doi: 10.1016/j.bbamem.2011.07.022 21819968

53. Nagle JF, Tristram-Nagle S. Structure of lipid bilayers. BBA-Rev Biomembranes. 2000;1469(3):159–195.

54. Armstrong CL, Barrett MA, Hiess A, Salditt T, Katsaras J, Shi AC, et al. Effect of Cholesterol on the Lateral Nanoscale Dynamics of Fluid Membranes. Eur Biophys J. 2012;41(10):901–913. doi: 10.1007/s00249-012-0826-4 22729214

55. Modig K, Pfrommer BG, Halle B. Temperature-dependent hydrogen-bond geometry in liquid water. Physical review letters. 2003;90(7):075502. doi: 10.1103/PhysRevLett.90.075502 12633241

56. Severcan F, Sahin I, Kazancı N. Melatonin strongly interacts with zwitterionic model membranes—evidence from Fourier transform infrared spectroscopy and differential scanning calorimetry. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2005;1668(2):215–222. doi: 10.1016/j.bbamem.2004.12.009

57. Ytreberg FM, Swendsen RH, Zuckerman DM. Comparison of free energy methods for molecular systems. The Journal of chemical physics. 2006;125(18):184114. doi: 10.1063/1.2378907 17115745

58. Laio A, Parrinello M. Escaping free-energy minima. Proceedings of the National Academy of Sciences. 2002;99(20):12562–12566. doi: 10.1073/pnas.202427399

59. Yang J, Calero C, Bonomi M, Martí J. Specific ion binding at phospholipid membrane surfaces. J Chem Theor Comput. 2015;11(9):4495–4499. doi: 10.1021/acs.jctc.5b00540

60. Senn HM, Thiel W. QM/MM methods for biological systems. In: Atomistic approaches in modern biology. Springer-Verlag Berlin Heidelberg; 2006. p. 173–290.

61. Martí J, Csajka FS, Chandler D. Stochastic transition pathways in the aqueous sodium chloride dissociation process. Chem Phys Lett. 2000;328(1):169–176.

62. Bolhuis PG, Chandler D, Dellago C, Geissler PL. Transition path sampling: Throwing ropes over rough mountain passes, in the dark. Annu Rev Phys Chem. 2002;53(1):291–318. doi: 10.1146/annurev.physchem.53.082301.113146 11972010

63. Martí J, Csajka FS. Transition path sampling study of flip-flop transitions in model lipid bilayer membranes. Physical Review E. 2004;69(6):061918. doi: 10.1103/PhysRevE.69.061918

64. Dellago C, Bolhuis PG. Transition path sampling and other advanced simulation techniques for rare events. In: Advanced Computer Simulation Approaches for Soft Matter Sciences III. Springer; 2009. p. 167–233.

65. Chandler D. Introduction to Modern Statistical Mechanics. Oxford University Press; 1987.

66. Florio GM, Zwier TS. Solvation of a flexible biomolecule in the gas phase: the ultraviolet and infrared spectroscopy of melatonin- water clusters. The Journal of Physical Chemistry A. 2003;107(7):974–983. doi: 10.1021/jp027053i

67. Barducci A, Bussi G, Parrinello M. Well-tempered metadynamics: a smoothly converging and tunable free-energy method. Phys Rev Lett. 2008;100(2):020603. doi: 10.1103/PhysRevLett.100.020603 18232845

68. Martí J, Guardia E, Padró J. Dielectric properties and infrared spectra of liquid water: Influence of the dynamic cross correlations. J Chem Phys. 1994;101(12):10883–10891. doi: 10.1063/1.467838

69. Praprotnik M, Janežič D. Molecular dynamics integration and molecular vibrational theory. III. The infrared spectrum of water. J Chem Phys. 2005;122(17):174103. doi: 10.1063/1.1884609 15910019

70. Martí J, Padró J, Guardia E. Computer simulation of molecular motions in liquids: Infrared spectra of water and heavy water. Molecular Simulation. 1993;11(6):321–336. doi: 10.1080/08927029308022517

71. Pieta E, Paluszkiewicz C, Oćwieja M, Kwiatek WM. Potential drug–nanosensor conjugates: Raman, infrared absorption, surface–enhanced Raman, and density functional theory investigations of indolic molecules. Applied Surface Science. 2017;404:168–179. doi: 10.1016/j.apsusc.2017.01.270

72. Singh G, Abbas J, Dogra SD, Sachdeva R, Rai B, Tripathi S, et al. Vibrational and electronic spectroscopic studies of melatonin. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2014;118:73–81. doi: 10.1016/j.saa.2013.08.077

73. Fleming GD, Koch R, Perez JM, Cabrera JL. Raman and SERS study of N-acetyl-5-methoxytryptamine, melatonin—The influence of the different molecular fragments on the SERS effect. Vibrational Spectroscopy. 2015;80:70–78. doi: 10.1016/j.vibspec.2015.08.002

74. Padró JA, Martí J. Response to “Comment on ‘An interpretation of the low-frequency spectrum of liquid water’” [J. Chem. Phys. 118, 452 (2003)]. The Journal of Chemical Physics. 2004;120(3):1659–1660. doi: 10.1063/1.1634252


Článek vyšel v časopise

PLOS One


2019 Číslo 11