Inhibition of IAPP and IAPP((20-29)) Fibrillation by Polymeric Nanoparticles

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Abstract

The fibrillation process of the islet amyloid polypeptide (IAPP) and its fragment (IAPP((20-29))) was studied by means of Thioflavin T (ThT) fluorescence and transmission electron microscopy in the absence and presence of N-isopropylacrylamide:N-tert-butylacrylamide (NiPAM:BAM) copolymeric nanoparticles. The process was found to be strongly affected by the presence of the nanoparticles, which retard protein fibrillation its a function of the chemical surface properties of the nanoparticles. The NiPAM:BAM ratio was varied front 50:50 to 100:0, The nanoparticles with higher fraction of NiPAM imposed the strongest retardation of IAPP and IAPP((20-29)) fibrillation. These particles have the strongest hydrogen bonding capacity due to the less bulky N-isopropyl group and thus less steric hindrance of the hydrogen-bonding groups of the nanoparticle polymer backbone. Kinetic fibrillation data, as monitored by ThT fluorescence and supported by surface plasmon resonance experiments, suggest that the peptide is strongly absorbed onto the surface of the nanoparticles. This interaction reduces the concentration of peptide free in solution available to proceed to fibrillation which results in an increased lag time of fibrillation, observed its it delayed onset of ThT fluorescence increase, plus it reduction of the amount of fibrils formed its indicated by the equilibrium values at the end of the fibrillation reaction. For the fragment (IAPP((20-29))) the presence of nanoparticles changes the mechanism of association from monomers to fibrils, by interfering with early oligomeric species along the fibrillation pathway.

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  • Biological Sciences
  • Physical Chemistry
Original languageEnglish
Pages (from-to)3453-3461
JournalLangmuir
Volume26
Issue number5
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes