title: The effect of nanoparticles on amyloid aggregation depends on the protein stability and intrinsic aggregation rate.
abstract: Nanoparticles interfere with protein amyloid formation. Catalysis of the process may occur due to increased local protein concentration and nucleation on the nanoparticle surface, whereas tight binding or a large particle/protein surface area may lead to inhibition of protein aggregation. Here we show a clear correlation between the intrinsic protein stability and the nanoparticle effect on the aggregation rate. The results were reached for a series of five mutants of single-chain monellin differing in intrinsic stability toward denaturation, for which a correlation between protein stability and aggregation propensity has been previously documented by Szczepankiewicz et al. [Mol. Biosyst.20107 (2), 521-532]. The aggregation process was monitored by thioflavin T fluorescence in the absence and presence of copolymeric nanoparticles with different hydrophobic characters. For mutants with a high intrinsic stability and low intrinsic aggregation rate, we find that amyloid fibril formation is accelerated by nanoparticles. For mutants with a low intrinsic stability and high intrinsic aggregation rate, we find the opposite--a retardation of amyloid fibril formation by nanoparticles. Moreover, both catalytic and inhibitory effects are most pronounced with the least hydrophobic nanoparticles, which have a larger surface accessibility of hydrogen-bonding groups in the polymer backbone.
authors.affiliation: Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, Lund, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Cabaleiro-Lago
authors.forename: O
authors.initials: O
authors.lastname: Szczepankiewicz
authors.forename: S
authors.initials: S
authors.lastname: Linse
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics; D052160:Benzothiazoles; D005453:Fluorescence; D006860:Hydrogen Bonding; D053758:Nanoparticles / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics; D055550:Protein Stability; D013844:Thiazoles / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D000178:Acrylamides; D000682:Amyloid; D052160:Benzothiazoles; D010940:Plant Proteins; D013844:Thiazoles; D014753:Vinyl Compounds; C002541:monellin protein, Dioscoreophyllum cumminsii; C009462:thioflavin T; C115287:tert-butylacrylamide