Origin of enthalpic depletion forces

Liel Sapir, Daniel Harries*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Solutes excluded from macromolecules or colloids are known to drive depletion attractions. The established Asakura-Oosawa model, as well as subsequent theories aimed at explaining the effects of macromolecular crowding, attribute depletion forces to diminished hard-core excluded volume upon compaction, and hence predict depletion forces dominated by entropy. However, recent experiments measuring the effect of preferentially excluded solutes on protein folding and macromolecular association find these forces can also be enthalpic. We use simulations of macromolecular association in explicit binary cosolute-solvent mixtures, with solvent and cosolute intermolecular interactions that go beyond hard-cores, to show that not all cosolutes conform to the established entropically dominated model. We further demonstrate how the enthalpically dominated depletion forces that we find can be well described within an Asakura-Oosawa like model provided that the hard-core macromolecule-cosolute potential of mean force is augmented by a "soft" step-like repulsion.

Original languageAmerican English
Pages (from-to)1061-1065
Number of pages5
JournalJournal of Physical Chemistry Letters
Issue number7
StatePublished - 3 Apr 2014


  • colloids
  • depletion attraction
  • effective forces
  • excluded cosolutes
  • macromolecular crowding
  • osmolytes


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