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Nano Research

Article Title

Graphene quantum dots rescue protein dysregulation of pancreatic β-cells exposed to human islet amyloid polypeptide

Authors

Ava Faridi, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
Yunxiang Sun, Department of Physics, Ningbo University, Ningbo 315211, China Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, USA
Monika Mortimer, Institute of Environmental and Health Sciences, College of Quality and Safety Engineering, China Jiliang University, Hangzhou 310018, China
Ritchlynn R. Aranha, Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
Aparna Nandakumar, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
Yuhuan Li, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
Ibrahim Javed, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
Aleksandr Kakinen, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
Qingqing Fan, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
Anthony W. Purcell, Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
Thomas P. Davis, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane Qld 4072, Australia
Feng Ding, Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, USA
Pouya Faridi, Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
Pu Chun Ke, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia

Keywords

islet amyloid polypeptide (IAPP), oligomer, amyloid, protein expression, graphene quantum dot

Abstract

The amyloid aggregation of peptides and proteins is a hallmark of neurological disorders and type 2 diabetes. Human islet amyloid polypeptide (IAPP), co-secreted with insulin by pancreatic β-cells, plays dual roles in both glycemic control and the pathology of type 2 diabetes. While IAPP can activate the NLRP3 inflammasome and modulate cellular autophagy, apoptosis and extracellular matrix metabolism, no data is available concerning intracellular protein expression upon exposure to the polypeptide. More surprisingly, how intracellular protein expression is modulated by nanoparticle inhibitors of protein aggregation remains entirely unknown. In this study, we first examined the changing proteomes of βTC6, a pancreatic β-cell line, upon exposure to monomeric, oligomeric and fibrillar IAPP, and detailed cellular protein expression rescued by graphene quantum dots (GQDs), an IAPP inhibitor. We found that 29 proteins were significantly dysregulated by the IAPP species, while majority of these proteins were nucleotide-binding proteins. Collectively, our liquid chromatography tandem–mass spectrometry, fluorescence quenching, helium ion microscopy, cytotoxicity and discreet molecular dynamics simulations data revealed a remarkable capacity of GQDs in regulating aberrant protein expression through H-bonding and hydrophobic interactions, pointing to nanomedicine as a new frontier against human amyloid diseases.

Graphical Abstract

Publisher

Tsinghua University Press

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