459248 Two-Step Crystal Nucleation Is Selected Because of Lower Surface Free Energy Barrier

Thursday, November 17, 2016: 8:55 AM
Cyril Magnin III (Parc 55 San Francisco)
Peter Vekilov, Chemical & Biomolecular Engineering, University of Houston, Houston, TX

Nucleation of crystals from solution underlies multitudinous natural and engineered processes. The formation of a crystal nucleus in a supersaturated environment creates an energy-rich interface. According to classical theory, the associated surface free energy barrier is overcome by random fluctuations leading to direct assembly of monomers into a crystalline embryo. Discrepancies between classical predictions and experimental observations suggested a two-step mechanism of crystal nucleation, whereby nuclei are hosted by disordered solute-rich precursors. A fundamental controversy of two-step nucleation is that whereas precursor populations often occupy a minor volume, nucleation confined to precursors is faster than direct nucleation. Here we demonstrate that nucleation of insulin crystals, which occurs with a highly regulated rate in mammalian pancreases as a part of insulin biosynthesis, is assisted by protein-rich clusters of radius 160 – 200 nm that occupy ca. 10-6 of the solution volume. We show that the surface free energy encountered by newly nucleated crystals is ca. 80-fold lower than the independently determined surface free energy of the crystal-solution interface; the latter value dictates the barrier for direct crystal nucleation in the solution. This comparison indicates that two-step nucleation is faster than the direct pathway and is selected as a phase transformation route due to a lower surface free energy barrier and suggests that nucleation of crystals can be controlled by manipulating the properties of the disordered precursors.

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See more of this Session: Nucleation and Growth I
See more of this Group/Topical: Separations Division