Constant-pressure molecular dynamics investigation of cholesterol effects in a dipalmitoylphosphatidylcholine bilayer.

We report a 1.4-ns constant-pressure molecular dynamics simulation of cholesterol at 12.5 mol% in a dipalmitoylphosphatidylcholine (DPPC) bilayer at 50 degrees C and compare the results to our previous simulation of a pure DPPC bilayer. The interlamellar spacing was increased by 2.5 A in the cholesterol-containing bilayer, consistent with x-ray diffraction results, whereas the bilayer thickness was increased by only 1 A. The bilayer/water interface was more abrupt because the lipid headgroups lie flatter to fill spaces left by the cholesterol molecules. This leads to less compensation by the lipid headgroups of the oriented water contribution to the membrane dipole potential and could explain the experimentally observed increase in the magnitude of the dipole potential by cholesterol. Our calculations suggested that 12.5 mol% cholesterol does not significantly affect the conformations and packing of the hydrocarbon chains and produces only a slight reduction in the empty free volume. However, cholesterol has a significant influence on the subnanosecond time scale lipid dynamics: the diffusion constant for the center-of-mass "rattling" motion was reduced by a factor of 3, and the reorientational motion of the methylene groups was slowed along the entire length of the hydrocarbon chains.

[1]  R. McElhaney,et al.  Physical studies of cholesterol-phospholipid interactions , 1996 .

[2]  B. Brooks,et al.  Effect of Electrostatic Force Truncation on Interfacial and Transport Properties of Water , 1996 .

[3]  H P Weber,et al.  Crystal structure and thermal vibrations of cholesteryl acetate from neutron diffraction at 123 and 20 K. , 1991, Acta crystallographica. Section B, Structural science.

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

[5]  A. Carruthers,et al.  Study of the relationship between bilayer water permeability and bilayer physical state , 1983 .

[6]  W. Hubbell,et al.  The membrane dipole potential in a total membrane potential model. Applications to hydrophobic ion interactions with membranes. , 1986, Biophysical journal.

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

[8]  B. Craven.  Pseudosymmetry in cholesterol monohydrate , 1979 .

[9]  S H White,et al.  Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. III. Complete structure. , 1992, Biophysical journal.

[10]  Douglas J. Tobias,et al.  Atomic-scale molecular dynamics simulations of lipid membranes , 1997 .

[11]  G Büldt,et al.  Neutron diffraction studies on phosphatidylcholine model membranes. I. Head group conformation. , 1979, Journal of molecular biology.

[12]  James H. Davis,et al.  Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures: 2H nuclear magnetic resonance and differential scanning calorimetry. , 1990, Biochemistry.

[13]  H. Berendsen,et al.  Free volume properties of a simulated lipid membrane , 1996 .

[14]  Richard W. Pastor,et al.  Molecular dynamics and Monte Carlo simulations of lipid bilayers , 1994 .

[15]  T. McIntosh,et al.  Cholesterol modifies the short-range repulsive interactions between phosphatidylcholine membranes. , 1989, Biochemistry.

[16]  E. Oldfield,et al.  Spectroscopic studies of specifically deuterium labeled membrane systems. Nuclear magnetic resonance investigation of the effects of cholesterol in model systems. , 1978, Biochemistry.

[17]  D. Mitov,et al.  Bending elasticities of model membranes: influences of temperature and sterol content. , 1997, Biophysical journal.

[18]  V A Parsegian,et al.  Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces. , 1992, Biophysical journal.

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

[20]  T. Xiang,et al.  Permeability of acetic acid across gel and liquid-crystalline lipid bilayers conforms to free-surface-area theory. , 1997, Biophysical journal.

[21]  Douglas J. Tobias,et al.  Constant Pressure and Temperature Molecular Dynamics Simulations of Crystals of the Lecithin Fragments: Glycerylphosphorylcholine and Dilauroylglycerol , 1995 .

[22]  H. Shieh,et al.  The structure of cholesterol , 1981 .

[23]  Herman J. C. Berendsen,et al.  Simulation of Water Transport through a Lipid Membrane , 1994 .

[24]  S. Hui,et al.  Molecular organization in cholesterol-lecithin bilayers by X-ray and electron diffraction measurements. , 1983, Biochemistry.

[25]  E. Oldfield,et al.  Deuterium nuclear magnetic resonance investigation of dimyristoyllecithin--dipalmitoyllecithin and dimyristoyllecithin--cholesterol mixtures. , 1979, Biochemistry.

[26]  S. Feller,et al.  Determination of component volumes of lipid bilayers from simulations. , 1997, Biophysical journal.

[27]  R. Gabdoulline,et al.  Comparison of the Structures of Dimyristoylphosphatidylcholine in the Presence and Absence of Cholesterol by Molecular Dynamics Simulations , 1996 .

[28]  J. Seelig,et al.  The dynamic structure of fatty acyl chains in a phospholipid bilayer measured by deuterium magnetic resonance. , 1974, Biochemistry.

[29]  E. Sackmann,et al.  Molecular and collective dynamics of lipid bilayers , 1996 .

[30]  W. Richards,et al.  Behavior of cholesterol and its effect on head group and chain conformations in lipid bilayers: a molecular dynamics study. , 1995, Biophysical journal.

[31]  J. Banavar,et al.  Computer Simulation of Liquids , 1988 .

[32]  R M Venable,et al.  Molecular dynamics simulations of a lipid bilayer and of hexadecane: an investigation of membrane fluidity. , 1993, Science.

[33]  T. Straatsma,et al.  THE MISSING TERM IN EFFECTIVE PAIR POTENTIALS , 1987 .

[34]  Donald E. Williams.  Nonbonded Potential Parameters Derived from Crystalline Hydrocarbons , 1967 .