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Evidence for different in vitro oligomerization behaviors of synthetic hIAPP obtained from different sources

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Abstract

Type 2 diabetes is characterized by the aggregation of human islet amyloid polypeptide (hIAPP), from monomer to amyloid deposits that are made of insoluble fibrils. Discrepancies concerning the nature of formed species or oligomerization kinetics among reported in vitro studies on hIAPP aggregation process have been highlighted. In this work, we investigated if the sample itself could be at the origin of those observed differences. To this aim, four hIAPP samples obtained from three different sources or suppliers have been analyzed and compared by ThT fluorescence spectroscopy and by two recently developed techniques, capillary electrophoresis (CE), and ESI-IMS-QToF-MS. Lots provided by the same supplier were shown to be very similar whatever the analytical technique used to characterize them. In contrast, several critical differences could be pointed out for hIAPP provided by different suppliers. We demonstrated that in several samples, some oligomerized peptides (e.g., dimer) were already present upon reception. Purity was also different, and the proneness of the peptide solution to form fibrils in vitro within 24 h could vary considerably from one sample source to another but not from lot to lot of the same source. All those results demonstrate that the initial state of conformation, oligomerization, and quality of the hIAPP can greatly impact the aggregation kinetics, and thus the information provided by these in vitro tests. Finally, a careful selection of the peptide batch and source is mandatory to perform relevant in vitro studies on hIAPP oligomerization and to screen new molecules modulating this pathological process.

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Funding

This work was supported by a public grant overseen by the French National Research Agency (ANR) as part of the “Investissement d’Avenir” program, through the “IDI 2015” project funded by the IDEX Paris-Saclay, ANR-11-IDEX-0003-02. This work was also supported by the DIM analytics from the Région Ile de France for MOBICS project funding.

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Authors and Affiliations

  1. CNRS, Institut Galien Paris Sud, Université Paris-Saclay, 92296, Châtenay-Malabry, France

    Corentin Berardet & Myriam Taverna

  2. CNRS, BioCIS, FLUOPEPIT, Université Paris-Saclay, 92290, Châtenay-Malabry, France

    Corentin Berardet, Julia Kaffy & Sandrine Ongeri

  3. Institut de Chimie Physique, UMR 8000, Réactivité des Ions, Spectrométrie de Masse, Analyse et Spectroscopies (RISMAS), CNRS, University Paris-Sud, University Paris-Saclay, Rue Henri Becquerel, Bâtiment 201 P2, 91405, Orsay, France

    Frédéric Halgand & Guillaume Van der Rest

  4. Institut Universitaire de France, Paris, France

    Myriam Taverna

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  1. Corentin Berardet
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Berardet, C., Kaffy, J., Halgand, F. et al. Evidence for different in vitro oligomerization behaviors of synthetic hIAPP obtained from different sources. Anal Bioanal Chem 412, 3103–3111 (2020). https://doi.org/10.1007/s00216-020-02560-5

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  • DOI: https://doi.org/10.1007/s00216-020-02560-5

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