On the ability of trehalose to offset the denaturing activity of urea

Experimental and computational studies indicate that trehalose offsets the denaturing activity of urea. According to a statistical thermodynamic model, the fundamental stabilizing contribution arises from the difference in the work to create a cavity suitable to host the D-state and the N-state, respectively. The magnitude of this solvent-excluded volume effect increases with aqueous solution density. Trehalose and urea addition to water leads to a density increase, that translates in an increase in the magnitude of the solvent-excluded volume effect which is so large to overwhelm the destabilizing contribution arising from the energetic attractions of urea with protein surface groups.