On the solvation of the phosphocholine headgroup in an aqueous propylene glycol solution

Abstract

The atomic-scale structure of the phosphocholine (PC) headgroup in 30 mol% propylene glycol (PG) in aqueous solution has been investigated using a combination of neutron diffraction with isotopic substitution experiments and computer simulation techniques -Molecular Dynamics and Empirical Potential Structure Refinement. Here, the hydration of the PC headgroup remains largely intact compared with the hydration of this group in a bilayer and in a bulk water solution, with the PG molecules showing limited interactions with the headgroup. When direct PG interactions with PC do occur, they are most likely to coordinate to the N(CH 3 ) + 3 motifs. Further, PG does not affect the bulk water structure and the addition of PC does not perturb the PG-solvent interactions. This suggests that the reason why PG is able to penetrate into membranes easily is that it does not form stronghydrogen bonding or electrostatic interactions with the headgroup allowing it to easily move across the membrane barrier.

On the hydration of DOPE in solution

“…19,20 This analysis method has been used to explore a range of chemical and biological solutions, [21][22][23][24][25][26][27][28][29][30] as well as specifically for the hydration of lipid molecules. 10,[12][13][14]31 Here EPSR simulations were performed on a box containing 10 DOPE, 50 H 2 O and 3000 CHCl 3 molecules at the temperature and atomic number density of the measurement (298 K and 0.0374 atoms/Å 3 ). The reference potentials used for DOPE (listed in Table I of the SI) are from the CHARMM36 forcefield 32 with its intramolecular geometry taken from the CHARMM-GUI online resource.…”

“…38 While this differs from the potentials used for EPSR, no major discrepancies between simulation results have been reported in previous studies on lipids from this, including when water is the bulk solvent. [12][13][14] The chloroform molecules were modeling using a model originally parameterised for the OPLS/AA forcefield 39 , which have been used in previous simulations of ceramide lipids in water and chloroform. 10 All of the bonds and angles for the water molecules were constrained using the SHAKE algorithm 40 .…”

“…Also, this study has investigated the role that water plays in bridging different parts of the lipid head groups within the same molecule and between two different lipid molecules. In doing so, a graph-theoretic (GT) approach is used to investigate the topological structure of interactions between the amine, phosphate and ester groups within the headgroup of In a similar way to previous work 14,45 , the GT framework is used to calculate the probability distribution of shortest through-water paths from each group in a lipid headgroup to any other group in a lipid headgroup. Then the probability distributions of the measured minimum paths connecting two groups in the PE headgroup on the same or different lipid molecules are determined.…”

“…46,47 Here, a set of orthonormal coordinates were assigned to both the water molecules, chloroform and different portions of the DOPE molecules (see SI Figure 2) to assess the 3-dimensional hydration structure around the DOPE headgroup by virtue of Spatial Density Maps (SDMs) vide infra. For EPSR, 5312 configuration files were collected for the subsequent analysis and 4005 snapshots of the MD trajectory were used as a comparison, comparable to number of frames used in ANGULA analyses on other lipids 11,14 . The maps show the location of molecules around a central group, with the scale bar representing the density of atoms perÅ 3 for a specified distance range and percentage.…”

“…10 Importantly, it has been recently shown that hydration studies of headgroups in such solutions serve as a good predictor of the hydration behavior within a membrane. 11 This combination of experimental and computational techniques have also been used to characterize the hydration of other prominent lipid headgroups which are present within biological membranes -including the PC headgroup, [12][13][14] and the sphingolipid ceramide 10 . This multidisciplinary approach is ideal for determining the atomic scale interactions between lipids and the surrounding aqueous solvents.…”