Surface-modified magnetite nanoparticles affect lysozyme amyloid fibrillization

Biochim Biophys Acta Gen Subj. 2021 Sep;1865(9):129941. doi: 10.1016/j.bbagen.2021.129941. Epub 2021 Jun 6.

Abstract

Background: The surface of nanoparticles (NPs) is an important factor affecting the process of poly/peptides' amyloid aggregation. We have investigated the in vitro effect of trisodium citrate (TC), gum arabic (GA) and citric acid (CA) surface-modified magnetite nanoparticles (COAT-MNPs) on hen egg-white lysozyme (HEWL) amyloid fibrillization and mature HEWL fibrils.

Methods: Dynamic light scattering (DLS) was used to characterize the physico-chemical properties of studied COAT-MNPs and determine the adsorption potential of their surface towards HEWL. The anti-amyloid properties were studied using thioflavin T (ThT) and tryptophan (Trp) intrinsic fluorescence assays, and atomic force microscopy (AFM). The morphology of amyloid aggregates was analyzed using Gwyddion software. The cytotoxicity of COAT-MNPs was determined utilizing Trypan blue (TB) assay.

Results: Agents used for surface modification affect the COAT-MNPs physico-chemical properties and modulate their anti-amyloid potential. The results from ThT and intrinsic fluorescence showed that the inhibitory activities result from the more favorable interactions of COAT-MNPs with early pre-amyloid species, presumably reducing nuclei and oligomers formation necessary for amyloid fibrillization. COAT-MNPs also possess destroying potential, which is presumably caused by the interaction with hydrophobic residues of the fibrils, resulting in the interruption of an interface between β-sheets stabilizing the amyloid fibrils.

Conclusion: COAT-MNPs were able to inhibit HEWL fibrillization and destroy mature fibrils with different efficacy depending on their properties, TC-MNPs being the most potent nanoparticles.

General significance: The study reports findings regarding the general impact of nanoparticles' surface modifications on the amyloid aggregation of proteins.

Keywords: Amyloid aggregation; Citric acid; Gum arabic; Hen egg-white lysozyme; Magnetite nanoparticles; Trisodium citrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / antagonists & inhibitors*
  • Amyloid / metabolism
  • Animals
  • Cells, Cultured
  • Chickens
  • Citrates / chemistry
  • Citrates / pharmacology*
  • Citric Acid / chemistry
  • Citric Acid / pharmacology*
  • Gum Arabic / chemistry
  • Gum Arabic / pharmacology*
  • HEK293 Cells
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • Muramidase / chemistry*
  • Particle Size
  • Protein Aggregates / drug effects
  • Surface Properties

Substances

  • Amyloid
  • Citrates
  • Magnetite Nanoparticles
  • Protein Aggregates
  • trisodium citrate
  • Citric Acid
  • Gum Arabic
  • hen egg lysozyme
  • Muramidase