A Protein Corona Modulates Interactions of α-Synuclein with Nanoparticles and Alters the Rates of the Microscopic Steps of Amyloid Formation

Hossein Mohammad-Beigi*, Masumeh Zanganeh, Carsten Scavenius, Hoda Eskandari, Azad Farzadfard, Seyed Abbas Shojaosadati, Jan J Enghild, Daniel E Otzen, Alexander K Buell, Duncan S Sutherland

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Nanoparticles (NPs) can modulate protein aggregation and fibril formation in the context of amyloid diseases. Understanding the mechanism of this action remains a critical next step in developing nanomedicines for the treatment or prevention of Parkinson's disease. α-Synuclein (α-Syn) can undergo interactions of different strength with nanoparticles, and these interactions can be prevented by the presence of a protein corona (PC) acquired during the exposure of NPs to serum proteins. Here, we develop a method to attach the PC irreversibly to the NPs, which enables us to study in detail the interaction of α-Syn and polyethylenimine-coated carboxyl-modified polystyrene NPs (PsNPs-PEI) and the role of the dynamics of the interactions. Analysis of the kinetics of fibril formation reveals that the NPs surface promotes the primary nucleation step of amyloid fibril formation without significantly affecting the elongation and fragmentation steps or the final equilibrium. Furthermore, the results show that even though α-Syn can access the surface of NPs that are precoated with a PC, due to the dynamic nature of the PC proteins, the PC nevertheless reduces the acceleratoring effect of the NPs. This effect is likely to be caused by reducing the overall amount of weakly interacting α-Syn molecules on the NP surface and the access of further α-Syn required for fibril elongation. Our experimental approach provides microscopic insight into how serum proteins can modulate the complex interplay between NPs and amyloid proteins.

Original languageEnglish
JournalACS Nano
Volume16
Issue1
Pages (from-to)1102-1118
Number of pages17
ISSN1936-0851
DOIs
Publication statusPublished - Jan 2022

Keywords

  • amyloid
  • kinetic of aggregation
  • microscopic steps
  • nanoparticle
  • protein corona
  • α-synuclein

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