The origin of depletion forces: entropy vs. enthalpy
Daniel Harries
Institute of Chemistry and The Fritz Haber Research Center
The Hebrew University, Jerusalem 91904, Israel
E-mail: daniel.harries@mail.huji.ac.il
Solutes preferentially excluded from macromolecules can drive depletion attractions
in important biological association processes. The established Asakura-Oosawa
theory relates depletion forces to the excluded volume reduction and the ensuing
entropy gain upon macromolecular compaction. Accordingly, cosolute-induced
protein stabilization is often described in terms of entropically driven “crowding”. In
agreement, many experiments of protein folding and other macromolecular
processes suggest that depletion forces are predominantly entropic for some
cosolutes, such as polyethylene glycol polymers. However, for other cosolutes, such
as polyol osmolytes, the effect is enthalpically dominated, while the entropic change
can even be unfavorable. Using the Kirkwood-Buff theory of solutions we
demonstrate that depletion forces can be quantified using the effective interaction
between cosolute and macromolecule. Specifically, by incorporating interactions
beyond hard-core, the depletion force attains considerable enthalpic contributions.
This analytic theory, supplemented by Monte-Carlo simulations, traces the origins of
enthalpically dominated depletion forces to "soft" cosolute-macromolecule repulsions.
Moreover, these depletion forces can be entropically disfavoured if the effective
cosolute-macromolecule interaction consistes of an entropic attractive component
and an enthalpic repulsive component. Finally, changes in excluded volume upon
compaction are found in the general case do not directly correspond to partial molar
volumes. These findings suggest a modified view of the role of excluded cosolutes on
macromolecular stabilization.