The influence of polyhydroxylated compounds on a hydrated phospholipid bilayer: a molecular dynamics study

Molecular dynamics simulations are used to investigate the interaction of the polyhydroxylated cosolutes ( CSLs) methanol ( MET), ethylene glycol ( ETG), glycerol ( GLY), glucose ( GLU) and trehalose ( TRH) with a hydrated phospholipid bilayer in the liquid-crystalline phase at 325 K. The comparison is performed at constant effective concentration of CSL hydroxyl groups. The results ( along with available experimental data) lead to the formulation of two distinct mechanisms for the interaction of polyhydroxylated compounds with lipid bilayers. The alcohol-like mechanism ( active for MET and ETG) involves preferential affinity of the CSL ( compared to water) for the superficial region of the bilayer interior, and is driven by the hydrophobic effect. It results in a lateral expansion of the membrane, a disorder increase within the bilayer, and a partial substitution of water by CSL molecules at the hydrogen-bonding sites provided by the membrane ( predominantly at the level of the ester groups). The sugar-like mechanism ( active for GLU and TRH) involves preferential affinity of the CSL ( compared to water) for the bilayer surface ( formation of a coating layer), and is driven by entropic effects. It results in the absence of lateral expansion and change in disorder within the bilayer, and in a partial substitution of water by CSL molecules ( predominantly at the level of the phosphate groups). It also involves the bridging of lipid molecules via hydrogen-bonded CSL molecules, a phenomenon that may have implications in the context of membrane stabilisation by sugars. Hydrogen bonding itself is not viewed as a driving force for these two mechanisms, which only involve the ( partial) substitution of water - lipid by CSL - lipid hydrogen bonds ( the sum of the two remaining essentially constant, irrespective of the nature and concentration of the CSL).