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 severalfold-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.biological function ͉ crystallization mechanisms ͉ in situ atomic force microscopy ͉ steps

Magnesite growth rates as a function of temperature and saturation state

“…(6) (Teng et al, 1999;Davis et al, 2000;Wasylenki et al, 2005). The first effect, the saturation dependent kink density, might be favored by the strong Mg-O bond energy (cf., Georgiou and Vekilov, 2006;Vekilov, 2007). The second effect, the influences of minute impurities, might be favored by the presence of impurities in the present study.…”

Mechanisms of hematin crystallization and inhibition by the antimalarial drug chloroquine

“…We used large β-hematin crystals prepared in the biomimetic CBSO solutions discussed above and performed, to our knowledge, the first time-resolved in situ AFM study of hematin crystal growth. In situ AFM has proven to be a valuable technique for elucidating structural and dynamic characteristics of classical and nonclassical crystallization mechanisms (38)(39)(40)(41). AFM topographical images (Fig.…”

Molecular Mechanisms of Hematin Crystallization from Organic Solvent

“…To elucidate the growth mechanism of hematin crystals, we employed time-resolved in situ AFM to image large crystals prepared as discussed in Olafson et al 65 In situ AFM has proven to be a valuable technique for clarifying structural and dynamic characteristics of classical and nonclassical crystallization mechanisms. 17,44,84,85 AFM topographical images of the (1̅ 00) hematin face in Figure 4 reveal the presence of unfinished layers with heights h = 1.17 ± 0.07 nm, close to the unit cell dimension in the [100] direction, a = 1.22 nm. 65 These images reveal that hematin crystals follow a classical mode of crystal growth, in which new layers are generated by 2D nucleation and spread to cover the entire facet.…”