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

• Published in: Langmuir Vol. 26; no. 5; pp. 3453 - 3461
• Main Authors: Cabaleiro-Lago, C, Lynch, I, Dawson, K. A, Linse, S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 02-03-2010
• Subjects: Acrylamides - chemistry; Acrylamides - metabolism; Acrylamides - pharmacology; aggregation; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; beta-protein; Biologi; Biological Interfaces: Biocolloids, Biomolecular and Biomimetic Materials; Biological Sciences; Chemical Sciences; Chemistry; Chromatography, Gel; Colloidal state and disperse state; Exact sciences and technology; fibrillogenesis; fibrils; full-length; Fysikalisk kemi; General and physical chemistry; Hydrogen Bonding; Islet amyloid polypeptide; Kemi; membrane disruption; Nanoparticles; Natural Sciences; Naturvetenskap; oligomers; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Physical and chemical studies. Granulometry. Electrokinetic phenomena; Physical Chemistry; Protein Binding - drug effects; protein fibrillation; Protein Multimerization - drug effects; Protein Structure, Quaternary; rat amylin; Surface physical chemistry; Surface Properties; Peptides; Retardation; Support; Hydrogen; Nanoparticle; Fluorescence; Steric hindrance; Polymer; Surface plasmon; Equilibrium; Fragment; Mechanism; Protein; Particle; Chemical reduction; Association; Transmission electron microscopy; Polypeptide; Surface properties; Resonance; Kinetics; Inhibition; Chemical properties; Monomer
• ISSN: 0743-7463; 1520-5827; 1520-5827
• DOI: 10.1021/la902980d

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.