Biological molecules as protectors against cellular damage caused by environmental extremes: The role of protectant-water interactions

Biological molecules, such as glycerol, sugars, amino acids and small proteins are known to serve as protectors against cellular damage in organisms caused by environmental extremes (dehydration, temperature and osmotic extremes). As environmental extremes all involve the status of water within cells, it is important to understand how biological molecules interact with water in their protective function. A combination of infrared spectroscopy and molecular dynamics simulations has been used to systematically study the effect of small biological molecules on surrounding water structure. The molecules examined---glycerol, six-carbon monosaccharides, and the disaccharides trehalose and maltose---all act as natural stress protectants and contain extensive hydroxylation that provides the ability to directly hydrogen bond and interact with water molecules in the surrounding hydration layer. These molecules were chosen as their structures represent a progression of hydroxyl group conformations from the flexible conformations found in glycerol to the more rigid conformations in mono- and disaccharides. The effect of these molecules on water structure was analyzed by examining concentration-dependent shifts in the OH stretch mode of infrared spectra as well as by determining the hydrogen bond angle distributions present in molecular dynamics simulations. The results reveal a number of important concepts. First, high glycerol concentrations disrupt the hydrogen bond network of water by interacting directly with surrounding water molecules through glycerol hydroxyl groups; glycerol molecules mimic the stronger interactions found between water molecules in the structure of ice, while preventing crystallization which can damage cell membranes. Next, the rigid conformation of cyclic monosaccharides allows for formation of cooperative intramolecular hydrogen bond networks which exhibit differing effects on surrounding water structure. Extensive intramolecular hydrogen bond networks reduce direct interaction of monosaccharides with water, thus disrupting water structure to a smaller extent than molecules lacking such networks. Although the disaccharides trehalose and maltose contain the same component monosaccharides, these molecules are able to exhibit slightly different abilities to modify surrounding water structure. Finally, while protectants influence water structure in vitro, their presence may not translate to observable effects in vivo. Insights gained from these experiments can be used in developing synthetic protectants for preservation and stabilization of food products and medicines.