Dense Liquid Precursor for the Nucleation of Ordered Solid Phases from Solution

Abstract

A line of recent theories and simulations have suggested that the nucleation of protein crystals might, under certain conditions, proceed in two steps: the formation of a droplet of a dense liquid, metastable with respect to the crystalline state, followed by ordering within this droplet to produce a crystal. In this review, I discuss experimental tests of the applicability of this mechanism to the nucleation of ordered solid phases: crystals or linear, planar, branched, or otherwise ordered aggregates of proteins and small molecule materials from solution. The main arguments stem from recent results on the kinetics of homogeneous nucleation of crystals of the protein lysozyme. These results indicate that under a very broad range of conditions the nucleation of lysozyme crystals occurs via a modification of the theoretically postulated mechanismas a superposition of fluctuations along the order parameters density and structure. Depending on whether the system is above or below its liquid−liquid coexiste...