Cofibrillization of Pathogenic and Functional Amyloid Proteins with Gold Nanoparticles against Amyloidogenesis

Biomacromolecules. 2017 Dec 11;18(12):4316-4322. doi: 10.1021/acs.biomac.7b01359. Epub 2017 Nov 14.

Abstract

Biomimetic nanocomposites and scaffolds hold the key to a wide range of biomedical applications. Here we show, for the first time, a facile scheme of cofibrillizing pathogenic and functional amyloid fibrils via gold nanoparticles (AuNPs) and their applications against amyloidogenesis. This scheme was realized by β-sheet stacking between human islet amyloid polypeptide (IAPP) and the β-lactoglobulin "corona" of the AuNPs, as revealed by transmission electron microscopy, 3D atomic force microscopy, circular dichroism spectroscopy, and molecular dynamics simulations. The biomimetic AuNPs eliminated IAPP toxicity, enabled X-ray destruction of IAPP amyloids, and allowed dark-field imaging of pathogenic amyloids and their immunogenic response by human T cells. In addition to providing a viable new nanotechnology against amyloidogenesis, this study has implications for understanding the in vivo cross-talk between amyloid proteins of different pathologies.

MeSH terms

  • Amyloid / chemistry
  • Amyloidogenic Proteins / chemistry*
  • Circular Dichroism / methods
  • Gold / chemistry*
  • Humans
  • Islet Amyloid Polypeptide / chemistry
  • Kinetics
  • Lactoglobulins / chemistry
  • Metal Nanoparticles / chemistry*
  • Microscopy, Atomic Force / methods
  • Microscopy, Electron, Transmission / methods
  • Molecular Dynamics Simulation
  • Nanotechnology / methods
  • Protein Conformation, beta-Strand
  • T-Lymphocytes / drug effects

Substances

  • Amyloid
  • Amyloidogenic Proteins
  • Islet Amyloid Polypeptide
  • Lactoglobulins
  • Gold