Macromolecular compaction by mixed solutions: Bridging versus depletion attraction

From colloidal dispersions to solvated polymers or proteins, solution composition is known to strongly influence the stable state of the bathing macromolecules. Mixed solvents containing species with different affinities to specific macromolecular states can shift equilibrium towards the thermodynamically preferred state with lower free energy, even when the molecular interactions with the solvent are weak. We review two known mechanisms, bridging and depletion attraction, and discuss how each can emerge, depending on the molecular size and interaction of the mixed solvent species. We show that simple theoretical considerations predict that the macromolecular state that is stabilized by each mechanism possesses unique structural properties, as well as distinct thermodynamic fingerprints. Furthermore, we demonstrate the mechanistic role of enthalpy and entropy, as seen in a simple mean field model of macromolecules in mixed solvents. These thermodynamic contributions determine the temperature dependence of cosolute induced effects. Finally, we review the possible role of fluctuations, and point to possible implications and open questions.