Proinsulin, a molecular precursor to insulin itself, is the reason for these crystals. After an insulin molecule is produced from proinsulin, it attaches to an insulin crystal only in special locations where other insulin molecules have formed right angles, called kinks. Using atomic-force microscopy, they discovered a new mechanism by which insulin molecules attach themselves to crystals to form these kinks. They found that groups of insulin blocks create large protrusions, dubbed "mounds" by Vekilov and Georgiou. The very nature of these mounds results in the creation of multiple kinks - far more, in fact, than other methods of kink formation.
By providing so many spaces where insulin molecules can attach to an insulin crystal, these mounds allow for the rapid growth of that crystal and only form when there is a surplus of insulin that allows for rapid crystal growth. Since no mounds appear when there is a lack of insulin and insulin crystals both grow and dissolve at kinks, mounds are important sources of a crystal's net growth.
"Typically in nature, fast growth also results in fast dissolution," Vekilov said. "But this process cheats physics because when there isn't a lot of insulin, mounds don't form. It's an asymmetric mechanism that has no balance."
While this discovery will play a significant role in gaining a better understanding of diabetes, it also is an historic find in the area of crystal formation and use, as only the third mechanism of crystal formation ever discovered. Before this finding, there were only two known ways that crystals grew - the first was proposed in 1876 and the second in 1968. Though the first and second discoveries, proposed by prominent American scientist and founder of modern thermodynamics J.W. Gibbs and by Russian scientist V.V. Voronkov, respectively, only recently demonstrated their applicability to real systems.Vekilov and Georgiou have already experimentally proved this latest mechanism in the work.
"It is possible that crystals composed of materials other than insulin also grow in this manner," Vekilov said. "If so, this discovery could significantly impact any number of fields that deal with crystals. It can help us understand all processes of crystal formation, including semiconductor and optical materials, geological crystallization, ice formation and the physiological and pathological crystallization of proteins and small molecules."
source:Eureka Alert
