Research Projects
Updated links to our lab's publications can be found at Othon Researchgate
Google Scholar Page: Christina Othon
Dynamical Regulation of Water by Small Molecules
Solvent molecules facilitate protein folding and conformational stability by acting as a plasticizer, and their role in regulating biomolecular structural dynamics cannot be overstated. Protein structure and activity in cells is carefully controlled by the relative concentration of small molecules called osmolytes, which influence protein structure indirectly by regulating water activity and hydration dynamics. We are interested in disaccharide osmoprotectants, in particular, because they appear to be unique in protecting protein structure from very diverse physical stresses including cryogenic temperatures, elevated temperature, dehydration, and excessive salinity (unlike, for example, protein chaperones that appear to be optimized for protection against specific environmental stressors). This property has led to the widespread use of disaccharide osmolytes in the cosmetic, food, and pharmaceutical industries. The physical mechanism behind osmoregulation is difficult to model and therefore nearly impossible to predict. Our research has directly measured the effect of disaccharide osmoprotectants on the hydration layer dynamics around a protein system. Our measurements differentiate between changes in solvation layer hydrogen bonding dynamics and bulk-like viscosity effects as predicted by the vitrification model.
Collective Dynamics in Lipid Structures
Biological lipid membranes are inherently dynamic which is essential to their ability to adapt to new particle insertion, for the sorting of membrane proteins, and for recycling material within the structure. Dynamic models, such as the lipid raft model, suggest that the nanoscale heterogeneity of lipid structures and dynamics function to drive protein sorting and self-assembly. We have observed a non-exponential reorientation correlation, indicating the presence of dynamic density clusters using time-resolved fluorescence microscopy. The dynamical changes are critically dependent upon both temperature and free volume, as would be expected by collective dynamics. These clusters could represent an essential physical feature responsible for controlling the rate of protein insertion and self-assembly in the cellular membrane.
Biophysical Interactions of Sucralose
Sucralose is a commonly employed artificial sweetener that appears to destabilize protein native structures. This is in direct contrast to the bio-preservative nature of its natural counterpart, sucrose, which enhances the stability of biomolecules against environmental stress. We explored the molecular interactions of sucralose as compared to sucrose to illuminate the origin of the differences in their bio-preservative efficacy. We show that the mode of interactions of sucralose and sucrose in bulk solution differ subtly through the use of hydration dynamics measurement and computational simulation. Sucralose does not appear to disturb the native state of proteins for moderate concentrations (< 0.2 M) at room temperature. However, as the concentration increases, or in the thermally stressed state, sucralose appears to differ in its interactions with protein leading to the reduction of native state stability. This difference in interaction appears weak. We explored the difference in the preferential exclusion model using time-resolved spectroscopic techniques and observed that both molecules appear to be effective reducers of bulk hydration dynamics. However, the chlorination of sucralose appears to slightly enhance the hydrophobicity of the molecule, which reduces the preferential exclusion of sucralose from the protein-water interface.
