Charge pairing of headgroups in phosphatidylcholine membranes: A molecular dynamics simulation study.

Molecular dynamics simulation of the hydrated dimyristoylphosphatidylcholine (DMPC) bilayer membrane in the liquid-crystalline phase was carried out for 5 ns to study the interaction among DMPC headgroups in the membrane/water interface region. The phosphatidylcholine headgroup contains a positively charged choline group and negatively charged phosphate and carbonyl groups, although it is a neutral molecule as a whole. Our previous study (Pasenkiewicz-Gierula, M., Y. Takaoka, H. Miyagawa, K. Kitamura, and A. Kusumi. 1997. J. Phys. Chem. 101:3677-3691) showed the formation of water cross-bridges between negatively charged groups in which a water molecule is simultaneously hydrogen bonded to two DMPC molecules. Water bridges link 76% of DMPC molecules in the membrane. In the present study we show that relatively stable charge associations (charge pairs) are formed between the positively and negatively charged groups of two DMPC molecules. Charge pairs link 93% of DMPC molecules in the membrane. Water bridges and charge pairs together form an extended network of interactions among DMPC headgroups linking 98% of all membrane phospholipids. The average lifetimes of DMPC-DMPC associations via charge pairs, water bridges and both, are at least 730, 1400, and over 1500 ps, respectively. However, these associations are dynamic states and they break and re-form several times during their lifetime.

[1]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 3. The van der Waals' potentials and crystal data for aliphatic and aromatic hydrocarbons , 1989 .

[2]  M. B. Kelly,et al.  Contribution of hydrogen bonding to lipid-lipid interactions in membranes and the role of lipid order: effects of cholesterol, increased phospholipid unsaturation, and ethanol. , 1993, Biochemistry.

[3]  M. Klein,et al.  Molecular dynamics investigation of the structure of a fully hydrated gel-phase dipalmitoylphosphatidylcholine bilayer. , 1996, Biophysical journal.

[4]  H. Casal,et al.  Quantitative determination of hydrocarbon chain conformational order in bilayers of saturated phosphatidylcholines of various chain lengths by Fourier transform infrared spectroscopy. , 1990, Biochemistry.

[5]  Conformations, orientations and time scales characterising dimyristoylphosphatidylcholine bilayer membrane. Molecular dynamics simulation studies. , 1997, Acta biochimica Polonica.

[6]  R. Wade,et al.  Exceptionally stable salt bridges in cytochrome P450cam have functional roles. , 1997, Biochemistry.

[7]  V. Parsegian,et al.  Hydration forces between phospholipid bilayers , 1989 .

[8]  Molecular Dynamics Investigation of the Lamellar Liquid-Crystal D-Phase in the Octylammonium Chloride/Water System , 1996 .

[9]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 1 , 1989 .

[10]  F. Jähnig,et al.  What is the surface tension of a lipid bilayer membrane? , 1996, Biophysical journal.

[11]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .

[12]  I. Sakurai,et al.  Lateral electrical conduction along a phosphatidylcholine monolayer. , 1987, Biochimica et biophysica acta.

[13]  C. Y. Lee,et al.  The surface tension of lipid water interfaces: Monte Carlo simulations , 1980 .

[14]  C. Ho,et al.  Hydration and order in lipid bilayers. , 1995, Biochemistry.

[15]  W. Hutton,et al.  Structure in the polar head region of phospholipid bilayers: a phosphorus-31 {proton} nuclear Overhauser effect study , 1976 .

[16]  G. Büldt,et al.  Zwitterionic dipoles as a dielectric probe for investigating head group mobility in phospholipid membranes. , 1978, Biochimica et biophysica acta.

[17]  M. Klein,et al.  Constant pressure and temperature molecular dynamics simulation of a fully hydrated liquid crystal phase dipalmitoylphosphatidylcholine bilayer. , 1995, Biophysical journal.

[18]  J. Nagle,et al.  Area/lipid of bilayers from NMR. , 1993, Biophysical journal.

[19]  R. Suter,et al.  X-ray structure determination of fully hydrated L alpha phase dipalmitoylphosphatidylcholine bilayers. , 1996, Biophysical journal.

[20]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[21]  F. A. Neugebauer,et al.  Structure and dynamics of phospholipid membranes: an electron spin resonance study employing biradical probes. , 1982, Biochemistry.

[22]  T. Lewis,et al.  ELECTRICAL INTERACTIONS IN PHOSPHOLIPID LAYERS , 1983 .

[23]  H. Frischleder,et al.  Quantum-chemical and statistical calculations on phospholipids , 1975 .

[24]  P. Meier,et al.  Chain configuration and flexibility gradient in phospholipid membranes. Comparison between spin-label electron spin resonance and deuteron nuclear magnetic resonance, and identification of new conformations. , 1989, Biophysical journal.

[25]  Lee G. Pedersen,et al.  Construction and molecular modeling of phospholipid surfaces , 1990 .

[26]  Terry R. Stouch,et al.  The limiting behavior of water hydrating a phospholipid monolayer: A computer simulation study , 1993 .

[27]  W. Hubbell,et al.  Molecular motion in spin-labeled phospholipids and membranes. , 1971, Journal of the American Chemical Society.

[28]  H. Berendsen,et al.  Molecular dynamics simulation of a charged biological membrane , 1996 .

[29]  Carlson,et al.  Theory of the ripple phase in hydrated phospholipid bilayers. , 1987, Physical review. A, General physics.

[30]  A. Darke,et al.  Deuteron magnetic resonance studies of water associated with phospholipids. , 1972, Chemistry and physics of lipids.

[31]  J. Teissié,et al.  Lateral proton conduction at a lipid/water interface. Effect of lipid nature and ionic content of the aqueous phase. , 1987, European journal of biochemistry.

[32]  B. Honig,et al.  Stability of "salt bridges" in membrane proteins. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[33]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[34]  J. Teissié,et al.  Lateral proton conduction in monolayers of phospholipids from extreme halophiles. , 1990, Biochemistry.

[35]  A. Kusumi,et al.  Hydrogen Bonding of Water to Phosphatidylcholine in the Membrane As Studied by a Molecular Dynamics Simulation: Location, Geometry, and Lipid-Lipid Bridging via Hydrogen-Bonded Water , 1997 .

[36]  M. Wilkins,et al.  Structure of oriented lipid bilayers. , 1971, Nature: New biology.

[37]  D. Eisenberg.  Proteins. Structures and molecular properties, T.E. Creighton. W. H. Freeman and Company, New York (1984), 515, $36.95 , 1985 .

[38]  H. Hauser,et al.  Preferred conformation and molecular packing of phosphatidylethanolamine and phosphatidylcholine. , 1981, Biochimica et biophysica acta.

[39]  H. Morgan,et al.  Models for interpreting surface potential measurements and their application to phospholipid monolayers , 1990 .

[40]  P. Yeagle.  Phospholipid headgroup behavior in biological assemblies , 1978 .

[41]  W. Hutton,et al.  Headgroup conformation and lipid--cholesterol association in phosphatidylcholine vesicles: a 31P(1H) nuclear Overhauser effect study. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[42]  G. Vanderkooi,et al.  Multibilayer structure of dimyristoylphosphatidylcholine dihydrate as determined by energy minimization. , 1991, Biochemistry.

[43]  Bernard R. Brooks,et al.  Computer simulation of liquid/liquid interfaces. I. Theory and application to octane/water , 1995 .

[44]  W. L. Jorgensen,et al.  The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. , 1988, Journal of the American Chemical Society.

[45]  W. Hutton,et al.  Phospholipid head-group conformations; intermolecular interactions and cholesterol effects. , 1977, Biochemistry.

[46]  L. Pratsch,et al.  Effect of poly(ethylene glycol) on phospholipid hydration and polarity of the external phase. , 1983, Biochimica et biophysica acta.