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European Biophysics Journal

, Volume 36, Issue 7, pp 711–715 | Cite as

Effects of confinement on insulin amyloid fibrils formation

  • Fabio LibrizziEmail author
  • Vito Foderà
  • Valeria Vetri
  • Caterina Lo Presti
  • Maurizio Leone
Original Paper

Abstract

Insulin, a 51-residue protein universally used in diabetes treatment, is known to produce amyloid fibrils at high temperature and acidic conditions. As for other amyloidogenic proteins, the mechanisms leading to nucleation and growth of insulin fibrils are still poorly understood. We here report a study of the fibrillation process for insulin confined in a suitable polymeric hydrogel, with the aim of ascertain the effects of a reduced protein mobility on the various phases of the process. The results indicate that, with respect to standard aqueous solutions, the fibrillation process is considerably slowed down at moderately high concentrations and entirely suppressed at low concentration. Moreover, the analysis of the initial stages of the fibrillation process in aqueous solutions revealed a large spatial heterogeneity, which is completely absent when the fibrillation is carried out in the hydrogel. We attribute this heterogeneity to the diffusion in solution of large amyloidal aggregates, which must be formed very fast compared to the average times for the whole sample. These findings are interpreted in the framework of recently suggested heterogeneous nucleation mechanisms. Moreover, they may be useful for the development of new insulin pharmaceutical formulations, more stable against adverse conditions.

Keywords

Insulin Amyloids Poly vinyl-alcohol Thioflavin T 

Notes

Acknowledgments

We acknowledge C. Dispenza and G. Spadaro for useful discussions, and G. Napoli for technical assistance. This work was partly supported by a national project (PRIN 2005) of the Italian Ministry of University and Research.

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Copyright information

© EBSA 2007

Authors and Affiliations

  • Fabio Librizzi
    • 1
    Email author
  • Vito Foderà
    • 1
    • 2
  • Valeria Vetri
    • 1
    • 2
  • Caterina Lo Presti
    • 3
  • Maurizio Leone
    • 1
    • 2
  1. 1.Dipartimento di Scienze Fisiche e AstronomicheUniversità di PalermoPalermoItaly
  2. 2.Istituto di Biofisica, Sezione di PalermoConsiglio Nazionale delle RicerchePalermoItaly
  3. 3.Dipartimento di Ingegneria Chimica dei Processi e dei MaterialiUniversità di PalermoPalermoItaly

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