  Recent studies suggest that cosolute mixtures may exert significant
non-additive effects upon protein stability. The corresponding liquid-vapor
interfaces may provide useful insight into these non-additive effects.
Accordingly, in this work we relate the interfacial properties of dilute
multicomponent solutions to the interactions between solutes. We first derive a
simple model for the surface excess of solutes in terms of thermodynamic
observables. We then develop a lattice-based statistical mechanical
perturbation theory to derive these observables from microscopic interactions.
Rather than adopting a random mixing approximation, this dilute solution theory
(DST) exactly treats solute-solute interactions to lowest order in perturbation
theory. Although it cannot treat concentrated solutions, Monte Carlo (MC)
simulations demonstrate that DST describes dilute solutions with much greater
accuracy than regular solution theory. Importantly, DST emphasizes an important
distinction between the `intrinsic' and `effective' preferences of solutes for
interfaces. DST predicts that three classes of solutes can be distinguished by
their intrinsic preference for interfaces. While the surface preference of
strong depletants are relatively insensitive to interactions, the surface
preference of strong surfactants can be modulated by interactions at the
interface. Moreover, DST predicts that the surface preference of weak
depletants and weak surfactants can be qualitatively inverted by interactions
in the bulk. We also demonstrate that DST can be extended to treat surface
polarization effects and to model experimental data. MC simulations validate
the accuracy of DST predictions for lattice systems that correspond to molar
concentrations.
