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

Abstract

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).

Conformational properties of glucose-based disaccharides investigated using molecular dynamics simulations with local elevation umbrella sampling

“…264 In the present work, trehalose appears special in two respects: (i) it is the least flexible disaccharide in the series (due to the influence of the exo-anomeric effect, in its most restrictive form for a-linkages, on its two glycosidic dihedral angles) and (ii) it presents a complete lack of intramolecular H-bonds (suggesting a high hydrophilicity). The low flexibility 147 is expected to enhance the affinity of the molecule for biostructures [273][274][275] (more limited entropy loss upon binding according to the sugar-like mechanism). The high hydrophilicity is expected to enhance the propensity for clustering and glass formation (self-association).…”

Interaction of the disaccharides trehalose and gentiobiose with lipid bilayers: A comparative molecular dynamics study

“…2. The headgroup-bridging hypothesis (HBH) is an extension of the WRH formulated based on simulations in the context of membrane bioprotection, which proposes that sugar molecules form a scaffold of H-bonds bridging multiple headgroups, thereby inhibiting a transition to the gel phase upon dehydration [29] (this scaffold is labile in the dilute regime [29,[41][42][43] but expected to strengthen upon dehydration, as a result of the removal of the water molecules competing for the headgroup Hbonding sites and of the reduction of dielectric screening effects). Trehalose (˛,˛-trehalose, TRH; Glc˛(1→1)˛Glc) is the non-reducing disaccharide consisting of two d-glucopyranose (Glc) residues in a˛(1→1)( two-bond, axial-axial) glycosidic linkage.…”

Cryopreservation of threatened native Australian species—what have we learned and where to from here?

“…glycerol, ethylene glycol and sorbitol) and sugars (e.g. sucrose) are providing insight at the molecular level of the interactions of these agents with phospholipid chains and headgroups and their effect on the liquid crystallinity and stability of biological membranes (Pereira and Hünenberger 2008). In addition, investigation of the vitrification properties of these cryoprotectants on liquid water is shedding light on the molecular mechanism of solvent cryoprotection by explaining changes to the glass transition temperature of water following the addition of cryoprotective agents (Kreck et al 2010).…”