Modulation of Dipalmitoylphosphatidylcholine Monolayers by Dimethyl Sulfoxide

Abstract

The action of the penetration-enhancing agent, dimethyl sulfoxide (DMSO), on phospholipid monolayers was investigated at the air-water interface using a combination of experimental techniques and molecular dynamics simulations. Brewster angle microscopy revealed that DPPC monolayers remained laterally homogeneous at subphase concentrations up to a mole fraction of 0.1 DMSO. Neutron reflectometry of the monolayers in combination with isotopic substitution enabled the determination of solvent profiles as a function of distance perpendicular to the interface for the different DMSO subphase concentrations. These experimental results were compared to those obtained from molecular dynamic (MD) simulations of the corresponding monolayer systems. There was excellent agreement found between the MD-derived reflectivity curves and the measured data for all of the H/D contrast variations investigated. The MD provide a detailed description of the distribution of water and DMSO molecules around the phosphatidylcholine headgroup, and how this distribution changes with increasing DMSO concentrations. Significantly, the measurements and simulations that are reported here support the hypothesis that DMSO acts by dehydrating the phosphatidylcholine headgroup, and as such provide the first direct evidence that it does so primarily by displacing water molecules bound to the choline group.

Assessing molecular simulation for the analysis of lipid monolayer reflectometry

“…The ESI also includes a Python class that is compatible with refnx [37,38] allowing for simulation-derived reflectometry profiles to be obtained, using a similar method to that employed in previous work, such as Dabkowska et al [18]. The Abelès matrix formalism is applied to layers, the SLD of which is drawn directly from the simulation, and the thickness of which is defined.…”

“…In all of the examples discussed so far there is no direct comparison between the reflectometry profile determined from simulation and that from the application of a traditional analysis method. Indeed, the only example, to the authors' knowledge where a direct comparison was drawn is the work of Dabkowska et al [18]. That work compares the reflectometry profile from a DPPC monolayer at the air-water interface containing dimethyl sulfoxide molecules with a similar molecular dynamics simulation parameterised with the CHARMM potential model.…”

Communication: Contrasting effects of glycerol and DMSO on lipid membrane surface hydration dynamics and forces

“…Neutron scattering measurements have shown a slight enrichment of DMSO near the surface, 21 which appears to be in agreement with IR measurements that suggest association of the partially charged atoms of DMSO (i.e., the positive sulfur and the negative oxygen) with either of the oppositely charged head group moieties of the phospholipid head group (i.e., the positive amine/choline and the negative phosphate). 28 In contrast, recent simulations have shown a ∼50% depletion of DMSO near the membrane surface, 29 which has been explained through a stronger preference of DMSO for water than the lipid. Differential vapor pressure and calorimetry measurements suggest that glycerol is preferentially excluded from the surface, and that its binding is thermodynamically unfavorable, 30 while simulations have shown a substantial enrichment.…”

Structure of surfactant and phospholipid monolayers at the air/water interface modeled from neutron reflectivity data

“…In one recent study the structure of a phospholipid monolayer was discussed with respect to changing surface pressure over the range 20-50 mN m -1 , 20 and in another an increase in density of the acyl chains layer with increasing surface pressure was discussed in the context of interactions with other species, 33 yet in both cases chain compaction with changing surface pressure was not considered explicitly. Other studies have also not taken into account this effect, 25,26 while in one study partial compaction of the acyl chains was implied by the parameters used although the effect was not discussed, 34 and in another it was discussed that a better fit to X-ray reflectivity data resulted using a higher density for the acyl chains although the reason was not resolved. 35 There are also studies involving neutron reflectivity data from supported bilayers at the solid/liquid interface in which this effect is either taken into account 36 or not.…”