Understanding the sol-gel transition in DSMO/lysozyme/water mixtures

A remarkably high viscosity has been induced in aqueous solutions of lysozyme by the addition of certain structurally related organic solvents, such as tetramethylurea (TMU), dimethylsulfoxide (DMSO), dimethylformamide (DMF), and hexamethylphosphortriamide. DMSO-induced gelation is observed in samples fulfilling the two following requirements: (1.) lysozyme concentration in excess of 5 mM, and (2.) volume fractions of DMSO exceeding 0.7. When both these critical values are exceeded, a sol-gel transition is found to take place leading to solid-like rheological behaviour instead of Newtonian behaviour. Various spectroscopic and calorimetric experiments performed under dilute conditions have led to a detailed picture of the conformational transitions that lysozyme undergoes upon increasing DMSO volume fraction in the mixtures. However, this is only part of the puzzle. Light scattering experiments indicate that the type of interactions between protein molecules are strongly dependent on both the protein and DMSO concentration. Currently, we are attempting to understand these changes in protein interactions based on our understanding of the conformation of the protein under dilute conditions and how these changes in interaction relate to a sol-gel transition at higher protein volume fractions and define the microstructure of the final gel. In this contribution, we will sketch a detailed physical picture of the conformation of lysozyme in aqueous DMSO mixtures under dilute conditions and discuss its consequences for the sol-gel transition and final gel microstructure at higher protein concentrations.