The curvature of gold nanoparticles influences the exposure of amyloid-beta and modulates its aggregation process

Tapia-Arellano, Andreas; Gallardo-Toledo, Eduardo; Celis, Freddy; Rivera, Rodrigo; Moglia, Italo; Campos, Marcelo; Carulla, Natalia; Baez, Mauricio; Kogan, Marcelo J.

Abstract

Gold nanoparticles (GNP) are tunable nanomaterials that can be used to develop rational therapeutic inhibitors against the formation of pathological aggregates of proteins. In the case of the pathological aggregation of the amyloid-beta protein (A beta), the shape of the GNP can slow down or accelerate its aggregation kinetics. However, there is a lack of elementary knowledge about how the curvature of GNP alters the interaction with the A beta peptide and how this interaction modifies key molecular steps of fibril formation. In this study, we analysed the effect of flat gold nanoprisms (GNPr) and curved gold nanospheres (GNS) on in vitro A beta 42 fibril formation kinetics by using the thioflavin-based kinetic assay and global fitting analysis, with several models of aggregation. Whereas GNPr accelerate the aggregation process and maintain the molecular mechanism of aggregation, GNS slow down this process and modify the molecular mechanism to one of fragmentation/secondary nucleation, with respect to controls. These results can be explained by a differential interaction between the A beta peptide and GNP observed by Raman spectroscopy. While flat GNPr expose key hydrophobic residues involved in the A beta peptide aggregation, curved GNS hide these residues from the solvent. Thus, this study provides mechanistic insights to improve the rational design of GNP nanomaterials for biomedical applications in the field of amyloid-related aggregation.

Más información

Título según WOS: The curvature of gold nanoparticles influences the exposure of amyloid-β and modulates its aggregation process
Título de la Revista: MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volumen: 128
Editorial: Multidisciplinary Digital Publishing Institute (MDPI)
Fecha de publicación: 2021
DOI:

10.1016/j.msec.2021.112269

Notas: ISI