Small polar molecules like glycerol and urea can preserve the fluidity of lipid bilayers under dry conditions

Glycerol and urea are examples of small, water-soluble molecules with low vapor pressure that can protect lipid membranes upon dehydration. Both are a part of the Natural Moisturizing Factor in human skin, and are also present in other organisms, where they prevent drying due to osmotic stress. This study was conducted in order to understand the mechanism of such protection. We have selected two ternary systems: dimyristoylphosphatidylcholine (DMPC)-glycerol-water and DMPC-urea-water, as models to investigate the molecular mechanisms behind this protective effect with a focus on factors that control the solid to liquid phase transition in the phospholipid bilayers. By combining a number of experimental techniques, including solid-state NMR, sorption microbalance and DSC, the structure and the phase transitions have been characterized at low water content and in excess solution. It was discovered that both glycerol and urea stabilize the liquid crystalline bilayers at low relative humidities (down to 75% RH at 27 degrees C), whereas for the pure DMPC-water system, a solid gel phase is induced at 93% RH. This demonstrates the protective effect of glycerol and urea against osmotic stress. It is further concluded that for lipid systems with limited access to solvent, the phase behavior is determined by solvent volume, irrespective of the composition. The observation that glycerol and urea have a similar effect on the lipid phase behavior under dry conditions, together with the lack of evidence of specific interactions between the lipids and glycerol or urea, implies a general mechanism, which might also be applicable to other, similar solutes.