A fast response mechanism for insulin storage in crystals may involve kink generation by association of 2D clusters.

Abstract

Crystals that are likely rhombohedral of Zn-insulin hexamers form in the islets of Langerhans in the pancreases of many mammals. The suggested functions of crystal formation is to protect the insulin from proteases and increase the degree of conversion of soluble proinsulin. To accomplish these ends, crystal growth should be fast and adaptable to rate fluctuations in the conversion reaction. Zn-insulin crystals grow layer by layer. Each layer spreads by the attachment of molecules to kinks located at the layers' edges, also called steps. The kinks are thought to be generated either by thermal fluctuations, as postulated by Gibbs, or by 1D nucleation of new crystalline rows. The kink density determines the rate at which steps advance, and these two kink-generation mechanisms lead to weak near-linear responses of the growth rate to concentration variations. We demonstrate for the crystallization of Zn-insulin a mechanism of kink generation whereby 2D clusters of several insulin molecules preformed on the terraces between steps associate to the steps. This mechanism results in several-fold-higher kink density, a faster rate of crystallization, and a high sensitivity of the kinetics to small increases of the solute concentration. If the found mechanism operates during insulin crystallization in vivo, it could be a part of the biological regulation of insulin production and function. For other crystallizing materials in biological and nonbiological systems, this mechanism provides an understanding of the often seen nonlinear acceleration of the kinetics.