Lecturer: Prof. Daniel Harries
Affiliation: Institute of Chemistry and The Fritz
Haber Research Center,
The Hebrew University of Jerusalem
Abstract:
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 to not
directly correspond to partial molar
volumes. These findings suggest a
modified view of the role of excluded
cosolutes on macromolecular
stabilization.