Inhibition of IAPP and IAPP(20-29) fibrillation by polymeric nanoparticles

Celia Cabaleiro-Lago, I Lynch, K A Dawson, S Linse

Forskningsoutput: TidskriftsbidragArtikelPeer review

116 Citeringar (Scopus)

Sammanfattning

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 as a function of the chemical surface properties of the nanoparticles. The NiPAM:BAM ratio was varied from 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 as a delayed onset of ThT fluorescence increase, plus a reduction of the amount of fibrils formed as 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.

OriginalspråkEngelska
Sidor (från-till)3453-3461
Antal sidor8
TidskriftLangmuir
Volym26
Utgåva5
DOI
StatusPublicerad - 2010
Externt publiceradJa

Nationell ämneskategori

  • Fysikalisk kemi (10402)

Fingeravtryck

Fördjupa i forskningsämnen för ”Inhibition of IAPP and IAPP(20-29) fibrillation by polymeric nanoparticles”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här