Structural Properties of Phospholipid-based Bilayers with Long-Chain Alcohol Molecules in the Gel Phase.

The structural properties of two-component gel-phase bilayers of distearylphosphatidylcholine (DSPC) and alcohol molecules with different compositions and chain lengths (12-24 carbons long) are studied via molecular dynamics simulations. Several bilayer properties, including area per lipid, tilt angle, chain interdigitation, and headgroup offset, are studied for each system and compared, revealing important structural implications depending upon headgroup size and chain length. While tail tilt is the primary mechanism for single-component bilayers to balance tail attraction and headgroup repulsion, our results demonstrate that the lipid mixtures studied adjust this balance via an offset between the depths of the different molecular species in the bilayer; this behavior is found to depend both on composition and on the length of alcohol molecules relative to the length of DSPC tails. It is shown that the structural properties of bilayers with asymmetric tail lengths depend strongly on the bilayer composition, while the composition has less influence on mixed-component bilayers with nearly symmetric tail lengths. These findings are explained on the basis of the interdigitation between bilayer leaflets and how interdigitation is related to other structural properties.

[1]  J. Nagle,et al.  Structure of gel phase DPPC determined by X-ray diffraction. , 2018, Chemistry and physics of lipids.

[2]  T. C. Moore,et al.  Investigating the Structure of Multicomponent Gel-Phase Lipid Bilayers. , 2016, Biophysical journal.

[3]  Massimo G Noro,et al.  Effect of monoglycerides and fatty acids on a ceramide bilayer. , 2016, Physical chemistry chemical physics : PCCP.

[4]  Kazuya Saito,et al.  Communication: Rigidification of a lipid bilayer by an incorporated n-alkane. , 2016, The Journal of chemical physics.

[5]  R. Böckmann,et al.  Biomembranes in atomistic and coarse-grained simulations , 2015, Journal of physics. Condensed matter : an Institute of Physics journal.

[6]  P. Coppock,et al.  Molecular Simulation of the DPPE Lipid Bilayer Gel Phase: Coupling between Molecular Packing Order and Tail Tilt Angle. , 2015, The journal of physical chemistry. B.

[7]  Kazuya Saito,et al.  Effect of n-alkanes on lipid bilayers depending on headgroups. , 2015, Chemistry and physics of lipids.

[8]  O. Edholm,et al.  Reparameterized United Atom Model for Molecular Dynamics Simulations of Gel and Fluid Phosphatidylcholine Bilayers. , 2014, Journal of chemical theory and computation.

[9]  Pramod C. Nair,et al.  An Automated Force Field Topology Builder (ATB) and Repository: Version 1.0. , 2011, Journal of chemical theory and computation.

[10]  Helgi I. Ingólfsson,et al.  Alcohol's effects on lipid bilayer properties. , 2011, Biophysical journal.

[11]  Massimo G Noro,et al.  Simulation studies of stratum corneum lipid mixtures. , 2009, Biophysical journal.

[12]  G. Feigenson,et al.  Effects of cholesterol and unsaturated DOPC lipid on chain packing of saturated gel-phase DPPC bilayers. , 2009, General physiology and biophysics.

[13]  G. Peters,et al.  Effects of fatty acid inclusion in a DMPC bilayer membrane. , 2009, The journal of physical chemistry. B.

[14]  P. Coppock,et al.  Atomistic simulations of mixed-lipid bilayers in gel and fluid phases. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[15]  J. Bouwstra,et al.  FTIR studies show lipophilic moisturizers to interact with stratum corneum lipids, rendering the more densely packed. , 2008, Biochimica et biophysica acta.

[16]  R. Böckmann,et al.  1-Alkanols and membranes: a story of attraction. , 2007, Biochimica et biophysica acta.

[17]  I. Vattulainen,et al.  What happens if cholesterol is made smoother: importance of methyl substituents in cholesterol ring structure on phosphatidylcholine-sterol interaction. , 2007, Biophysical journal.

[18]  R. Faller,et al.  How alcohol chain-length and concentration modulate hydrogen bond formation in a lipid bilayer. , 2007, Biophysical journal.

[19]  M. Bleckwenn,et al.  Interactions of anesthetics with their targets: non-specific, specific or both? , 2006, Pharmacology & therapeutics.

[20]  Perttu S. Niemelä,et al.  Influence of chain length and unsaturation on sphingomyelin bilayers. , 2006, Biophysical journal.

[21]  Chris Oostenbrink,et al.  A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force‐field parameter sets 53A5 and 53A6 , 2004, J. Comput. Chem..

[22]  M. Patra,et al.  Under the influence of alcohol: the effect of ethanol and methanol on lipid bilayers. , 2004, Biophysical journal.

[23]  M. Patra,et al.  Lessons of slicing membranes: interplay of packing, free area, and lateral diffusion in phospholipid/cholesterol bilayers. , 2004, Biophysical journal.

[24]  T. Engels,et al.  Molecular dynamics simulations of stratum corneum lipid models: fatty acids and cholesterol. , 2001, Biochimica et biophysica acta.

[25]  R. Templer,et al.  Phosphatidylcholine-fatty acid membranes: effects of headgroup hydration on the phase behaviour and structural parameters of the gel and inverse hexagonal (H(II)) phases. , 1997, Biochimica et biophysica acta.

[26]  R. Suter,et al.  Structure of gel phase saturated lecithin bilayers: temperature and chain length dependence. , 1996, Biophysical journal.

[27]  E. Jakobsson,et al.  Incorporation of surface tension into molecular dynamics simulation of an interface: a fluid phase lipid bilayer membrane. , 1995, Biophysical journal.

[28]  Steve Plimpton,et al.  Fast parallel algorithms for short-range molecular dynamics , 1993 .

[29]  G. S. Smith,et al.  X-ray structural studies of freely suspended ordered hydrated DMPC multimembrane films , 1990 .

[30]  W. R. Lieb,et al.  Partitioning of long-chain alcohols into lipid bilayers: implications for mechanisms of general anesthesia. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[31]  T. McIntosh,et al.  The organization of n-alkanes in lipid bilayers. , 1980, Biochimica et biophysica acta.

[32]  H. Mantsch,et al.  The gel phase of dipalmitoyl phosphatidylcholine. An infrared characterization of the acyl chain packing. , 1980, Biochimica et biophysica acta.

[33]  J M Sturtevant,et al.  Investigation of phase transitions of lipids and lipid mixtures by sensitivity differential scanning calorimetry. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Alexander P. Lyubartsev,et al.  Recent development in computer simulations of lipid bilayers , 2011 .

[35]  P. Westh,et al.  Packing properties of 1-alkanols and alkanes in a phospholipid membrane. , 2006, Biophysical chemistry.

[36]  Mark R. Wilson,et al.  Determination of order parameters in realistic atom-based models of liquid crystal systems , 1996 .

[37]  Robert C. Weast Jeanette G Grasselli David R. Lide,et al.  Handbook of data on organic compounds , 1994 .

[38]  J. Sturtevant,et al.  Investigation of phase transitions of lipids and lipid mixtures by high sensitivity differential scanning calorimetry ( lipid bilayers / membranes / phase diagrams / transition heat capacity curves ) , 2022 .