Molecular dynamics (MD) simulations have been used to investigate the interactions of a variety of hydroxylated cryosolvents (glycerol, propylene glycol and ethylene glycol), methanol and dimethyl sulfoxide (DMSO) in aqueous solution with a 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayer in its fluid phase at 323K. Each cryosolvent induced lateral expansion of the membrane leading to thinning of the bilayer and resulting in disordering of the lipid hydrocarbon chains. Propylene glycol and DMSO were observed to exhibit a greater disordering effect on the structure of the membrane than the other three alcohols. Closer examination exposed a number of effects on the lipid bilayer as a function of the molecular size and hydrogen bonding capacity of the cryosolvents. Analyses of hydrogen bonds revealed that increased concentrations of the polyhydroxylated cryosolvents induced the formation of a cross-linked cryosolvent layer across the surface of the membrane bilayer. This effect was most pronounced for glycerol at sufficiently high concentrations, which displayed a comparatively enhanced capacity to induce cross-linking of lipid headgroups resulting in the formation of extensive hydrogen bonding bridges and the promotion of a dense cryosolvent layer across the phospholipid bilayer.

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Sugar–membrane interactions are believed to be responsible for cell preservation during desiccation and freezing, but the molecular mechanism by which they achieve this is still not well understood. The associated decrease of the main phase transition temperature of phospholipid bilayers is explained by two opposing views on the matter: the direct sugar–phospholipid interaction at the bilayer interface (water replacement hypothesis) and an entropy-driven phase transition with sugar molecules concentrating away from the lipid interface (hydration forces explanation). Both mechanisms are supported by experiments but molecular dynamics (MD) simulations have overwhelmingly shown the occurrence of direct sugar–phospholipid interactions. We have performed MD simulations of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers at different water and sucrose contents. The behavior of sucrose was found to depend on both the sucrose and water contents: at high sucrose concentration and at low hydration, it is best described by the hydration forces explanation model, whereas at low sucrose concentration, it is consistent with the water replacement hypothesis model. These simulations reveal that at low concentration, sucrose molecules preferentially interact directly with the membrane interface while at high concentration, they preferentially accumulate in the intermembrane solution. The transition between the two modes of interaction is revealed for the first time as being governed by the saturation of the lipid bilayer interface with sucrose molecules, and this occurs more rapidly as the level of hydration decreases.

Polyhydroxylated alcohols and DMSO are common cryosolvents that can damage cell membranes at sufficiently high concentrations. The interaction of representative plant cell membranes composed of mixed 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-β-sitosterol bilayers, at a range of compositions, with a variety of cryosolvent molecules (DMSO, propylene glycol, ethylene glycol, glycerol, and methanol) has been investigated using molecular dynamics simulations. All the cryosolvents cause the bilayers to thin and become disordered; however, DMSO and propylene glycol have a greater disordering effect on the bilayer. Propylene glycol is shown to have the ability to cause the formation of pores in pure DOPC bilayers in a manner similar to that previously shown for DMSO. As the concentration of β-sitosterol within the bilayer increases, the membranes become more resistant to the deleterious effects of the cryosolvents. All three polyhydroxylated species are observed to form hydrogen bonds to multiple phospholipid molecules, effectively acting as cross-linkers, with glycerol being the most effective cross-linker. Increases in the concentration of β-sitosterol reduce overall hydrogen bonding of the bilayer with the cryosolvents as well as cross-linking, with glycerol and ethylene glycol being the most affected. The ability of all of these cryosolvents to affect the integrity of cell membranes appears to be the result of the balance of their ability to disorder lipid bilayers, to diffuse across them, and to interact with the lipid head groups.