The structural and dynamics properties of the bilayer comprising 128 molecules of dipalmitoylphosphatidylcholine (DPPC), dilauroylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), and distearoylphosphatidylcholine (DSPC) in water were investigated using a coarse-grained molecular dynamics (CG-MD) simulation technique. The model mixture system was simulated at 298？K under semi-isotropic pressure conditions. The aggregation was initiated from the random configurations followed by the formation of a bilayer over a period of 500？ns. The calculated values of the area per lipid, thickness, and lateral diffusion for the mixed model were different from when a single lipid was used. Our results confirmed that the chain length of the lipid molecules strongly affects the phospholipid bilayer’s physical properties. 1. Introduction Phospholipid bilayers are vital components of life and play a crucial role in membrane-mediated cell signaling [1]. A typical class of lipids is the phosphatidylcholines (PCs), which contains a family of saturated and symmetric phospholipids with the same molecular structures and different alkyl chain lengths. The alkyl chain lengths of PCs range from 12 carbon atoms in DLPC (1,2-dilauroyl-sn-glycero-3-phosphocholine) to 14 carbon atoms in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), 16 carbon atoms in DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), and 18 carbon atoms in DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) [2]. Phosphatidylcholines are considered as zwitterionic surfactant molecules due to the existence of two charged groups with different sizes. The anionic part involves phosphates, whereas the positive charge is located on the ammonium group [3]. Lipid molecules can exhibit micellar shapes, rod-like structures, and bilayers in aqueous solution due to their surfactant-like properties. The shape of the structure is usually dependent on the solution’s concentration, temperature, and physicochemical properties [4]. The self-assembly of PC molecules is important for nanoemulsion formulations [5, 6]. Both theoretical and experimental studies have demonstrated that nanoemulsions have great potential for application as drug carriers for transdermal drug delivery [7]. Phosphatidylcholines can spontaneously organize into bilayers due to their cylindrical shapes [8]. Figure 1 shows the molecular structures of DLPC (a), DMPC (b), DPPC (c), and DSPC (d). Figure 1: The structures of DLPC, DMPC, DPPC, and DSPC molecules. Traditional molecular dynamics (MD), which applies all-atom level or united-atom level
References
[1]
G. Weissmann and R. Clairborne, Cell Membranes: Biochemistry, Cell Biology and Pathology, H. P. Publishing, New York, NY, USA, 1975.
[2]
R. A. Walker, J. C. Conboy, and G. L. Richmond, “Molecular structure and ordering of phospholipids at a liquid-liquid interface,” Langmuir, vol. 13, no. 12, pp. 3070–3072, 1997.
[3]
M. A. Malik, M. A. Hashim, F. Nabi, S. A. AL-Thabaiti, and Z. Khan, “Anti-corrosion ability of surfactants: a review,” International Journal of Electrochemical Science, vol. 6, no. 6, pp. 1927–1948, 2011.
[4]
J. N. Israelachvili, Intermolecular and Surface Forces, Academic Press:, London, UK, 2nd edition, 1992.
[5]
V. Devarajan and V. Ravichandran, “Nanoemulsions: as modified drug delivery tool,” International Journal of Comprehensive Pharmacy, vol. 2, no. 04, 2011.
[6]
S. Zainol, M. Basri, H. Basri et al., “Formulation optimization of palm-based nanoemulsion system containing Levodopa,” International Journal of Molecular Sciences, vol. 13, no. 10, pp. 13049–13064, 2012.
[7]
R. A. Karjiban, M. Basri, M. B. Abdul Rahman, and A. B. Salleh, “Molecular dynamics simulation of palmitate ester self-assembly with diclofenac,” Internatinal Journal of Molecular Sciences, vol. 13, no. 8, pp. 9572–9583, 2012.
[8]
A. V. Frolov, A. V. Shnyrova, and J. Zimmerberg, “Lipid polymorphisms and membrane shape,” Cold Spring Harbor Perspectives in Biology, vol. 3, no. 11, Article ID 004747, 2011.
[9]
S. J. Marrink, H. J. Risselada, S. Yefimov, D. P. Tieleman, and A. H. De Vries, “The MARTINI force field: coarse grained model for biomolecular simulations,” Journal of Physical Chemistry B, vol. 111, no. 27, pp. 7812–7824, 2007.
[10]
J. C. Shelley, M. Y. Shelley, R. C. Reeder, S. Bandyopadhyay, and M. L. Klein, “A coarse grain model for phospholipid simulations,” Journal of Physical Chemistry B, vol. 105, no. 19, pp. 4464–4470, 2001.
[11]
S. J. Marrink, A. H. de Vries, and A. E. Mark, “Coarse grained model for semiquantitative lipid simulations,” Journal of Physical Chemistry B, vol. 108, no. 2, pp. 750–760, 2004.
[12]
R. Faller and S.-J. Marrink, “Simulation of domain formation in DLPC-DSPC mixed bilayers,” Langmuir, vol. 20, no. 18, pp. 7686–7693, 2004.
[13]
S. J. Marrink, J. Risselada, and A. E. Mark, “Simulation of gel phase formation and melting in lipid bilayers using a coarse grained model,” Chemistry and Physics of Lipids, vol. 135, no. 2, pp. 223–244, 2005.
[14]
E. Lindahl, B. Hess, and D. van der Spoel, “GROMACS 3.0: a package for molecular simulation and trajectory analysis,” Journal of Molecular Modeling, vol. 7, no. 8, pp. 306–317, 2001.
[15]
H. J. C. Berendsen, J. P. M. Postma, W. F. van Gunsteren, A. Dinola, and J. R. Haak, “Molecular dynamics with coupling to an external bath,” The Journal of Chemical Physics, vol. 81, no. 8, pp. 3684–3690, 1984.
[16]
M. P. Allen and D. J. Tildesley, Computer Simulation of Liquids, Oxford University Press, Oxford, UK, 1989.
[17]
N. Ku？erka, Y. Liu, N. Chu, H. I. Petrache, S. Tristram-Nagle, and J. F. Nagle, “Structure of fully hydrated fluid phase DMPC and DLPC lipid bilayers using x-ray scattering from oriented multilamellar arrays and from unilamellar vesicles,” Biophysical Journal, vol. 88, no. 4, pp. 2626–2637, 2005.
[18]
N. Ku？erka, J. F. Nagle, J. N. Sachs et al., “Lipid bilayer structure determined by the simultaneous analysis of neutron and X-ray scattering data,” Biophysical Journal, vol. 95, no. 5, pp. 2356–2367, 2008.
[19]
W. Humphrey, A. Dalke, and K. Schulten, “VMD: visual molecular dynamics,” Journal of Molecular Graphics, vol. 14, no. 1, pp. 33–38, 1996.
[20]
C. Tanford, The Hydrophobic Effect: Formation of Micelles and Biological Membranes, John Wiley and Sons, New York, NY, USA, 1980.
[21]
O. Edholm and J. F. Nagle, “Areas of molecules in membranes consisting of mixtures,” Biophysical Journal, vol. 89, no. 3, pp. 1827–1832, 2005.
[22]
M. Orsi and J. W. Essex, “Physical properties of mixed bilayers containing lamellar and nonlamellar lipids: insights from coarse-grain molecular dynamics simulations,” Faraday Discussions, vol. 161, pp. 249–272, 2013.
[23]
H. I. Petrache, S. W. Dodd, and M. F. Brown, “Area per lipid and acyl length distributions in fluid phosphatidylcholines determined by 2H NMR spectroscopy,” Biophysical Journal, vol. 79, no. 6, pp. 3172–3192, 2000.
[24]
N. Ku？erka, M.-P. Nieh, and J. Katsaras, “Fluid phase lipid areas and bilayer thicknesses of commonly used phosphatidylcholines as a function of temperature,” Biochimica et Biophysica Acta, vol. 1808, no. 11, pp. 2761–2771, 2011.
[25]
Q. Waheed and O. Edholm, “Undulation contributions to the area compressibility in lipid bilayer simulations,” Biophysical Journal, vol. 97, no. 10, pp. 2754–2760, 2009.
[26]
A. G. Lee, “How lipids affect the activities of integral membrane proteins,” Biochimica et Biophysica Acta, vol. 1666, no. 1-2, pp. 62–87, 2004.
[27]
T. J. McIntosh and S. A. Simon, “Hydration force and bilayer deformation: a reevaluation,” Biochemistry, vol. 25, no. 14, pp. 4058–4066, 1986.
[28]
N. Ku？erka, M. A. Kiselev, and P. Balgavy, “Determination of bilayer thickness and lipid surface area in unilamellar dimyristoylphosphatidylcholine vesicles from small-angle neutron scattering curves: a comparison of evaluation methods,” European Biophysics Journal, vol. 33, no. 4, pp. 328–334, 2004.
[29]
C. Hofs？？, E. Lindahl, and O. Edholm, “Molecular dynamics simulations of phospholipid bilayers with cholesterol,” Biophysical Journal, vol. 84, no. 4, pp. 2192–2206, 2003.
