Mechanism for the stabilization of protein clusters above the solubility curve

Abstract

Pan, Vekilov and Lubchenko [J. Phys. Chem. B, 2010, 114, 7620] have proposed that dense stable protein clusters appearing in weak protein solutions above the solubility curve are composed of protein oligomers. The hypothesis is that a weak solution of oligomer species is unstable with respect to condensation causing the formation of dense, oligomer-rich droplets which are stabilized against growth by the monomer–oligomer reaction. Here, we show that such a combination of processes can be understood using a simple capillary model yielding analytic expressions for the cluster properties which can be used to interpret experimental data. We also construct a microscopic Dynamic Density Functional Theory model and show that it is consistent with the predictions of the capillary model. The viability of the mechanism is thus confirmed and it is shown how the radius of the stable clusters is related to physically interesting quantities such as the monomer–oligomer rate constants.