(443f) Ostwald-Like Ripening of the Anomalous Mesoscopic Clusters in Protein Solutions

Anomalous clusters of mesoscopic dimensions composed of protein-rich liquid exist in protein solutions, both in the homogenous region of the solution phase diagram and in the region supersaturated with respect to an ordered solid phase, such as crystals.  They are of interest because in supersaturated solutions they are crucial nucleation sites for the ordered phase.  We monitor over 71 hours the evolution of the anomalous clusters in solutions of the protein lysozyme employing dynamic and static light scattering and Brownian microscopy.  For the sake of experimental clarity, we choose conditions, under which no condensed phases, liquid or solid, are stable or present as long-lived metastable domains.  We show that cluster formation is reversible and the clusters are in near equilibrium with the solution, up to a capillary correction.  We observe that en route to full equilibration, the average cluster size grows with time following a universal law t^0.26±0.03, independent of the cluster volume fraction.  We show that the cluster size distribution is scale-invariant at all stages of the cluster evolution.  These observations indicate that, similar to classical Ostwald ripening of new phases, cluster evolution is driven by minimization of the surface free energy and occurs by the exchange of single molecules.  The observed cluster evolution may help to understand nucleation mysteries, such as variable nucleation rates under steady conditions, and others.