2011.11.07,Professor Sun Lianhong Published a paper entitled “Multimerization and Aggregation of Native State Insulin: Effect of Zinc"in Langmuir

  • Author:Yisheng Xu, Yunfeng Yan, Daniel Seeman, Lianhong Sun, and Paul L Dubin

    Abstract:The aggregation of insulin is complicated by the coexistence of various multimers especially in thepresence of Zn2+. However, most investigations of insulin multimerization tend to overlookaggregation kinetics, while studies of insulin aggregation generally pay little attention tomultimerization. A clear understanding of the starting multimeric state of insulin is necessary for theelucidation of its aggregation mechanism. In this work, the native state aggregation of insulin eitheras the Zn-insulin hexamer or as the Zn-free dimer was studied by turbidimetry and dynamic lightscattering, at low ionic strength and pH near pI. These two states were achieved by varying the Zn2+content of insulin at low concentration, in accord with SEC results and with literature findings. Themuch greater aggregation rate and limiting turbidity (τ∞) for the Zn-insulin hexamer relative to theZn-free dimer was explained by their different aggregation mechanisms. Sequential first-orderkinetic regimes, and the concentration-dependence of τ∞ for Zn-hexamer indicate a nucleation andgrowth mechanism as proposed by Kurganov. The pure second-order process for the Zn-free dimersuggests an isodesmic aggregation consistent with the literature. The aggregation behavior atintermediate Zn2+ concentration appears to be the sum of the two processes.

    DOI: 10.1021/la202902a

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