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

► Trehalose offsets the denaturing activity of urea. ► The N-state is stabilized by the decrease in solvent-excluded volume. ► The magnitude of the latter depends upon the aqueous solution density. ► Addition of trehalose and urea leads to a density increase. ► The latter offsets the urea energetic attractions with protein surface.