Proline functionalized gold nanoparticles modulates lysozyme fibrillation

Srijeeb Karmakar; Nandini Sarkar; Lalit M Pandey

doi:10.1016/j.colsurfb.2018.11.032

Proline functionalized gold nanoparticles modulates lysozyme fibrillation

Colloids Surf B Biointerfaces. 2019 Feb 1:174:401-408. doi: 10.1016/j.colsurfb.2018.11.032. Epub 2018 Nov 20.

Authors

Srijeeb Karmakar¹, Nandini Sarkar², Lalit M Pandey³

Affiliations

¹ Bio-Interface & Environmental Engineering Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam, 781039, India; Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, 769008, Odisha, India. Electronic address: karma176106011@iitg.ac.in.
² Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, 769008, Odisha, India. Electronic address: sarkarn@nitrkl.ac.in.
³ Bio-Interface & Environmental Engineering Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam, 781039, India. Electronic address: lalitpandey@iitg.ac.in.

PMID: 30476794
DOI: 10.1016/j.colsurfb.2018.11.032

Abstract

Amyloid fibrils are the hallmarks of neurodegenerative diseases like Alzheimer's, Parkinson's and other proteopathies. Inhibition of fibrillation is a potential strategy to check the progress of amyloid associated diseases and further allied deterioration. In this study, we have synthesized proline functionalized gold nanoparticles (Pro-AuNPs) and scrutinized its antifibrillation property towards Hen Egg White Lysozyme (HEWL) aggregation. Pro-AuNPs were characterized using various biophysical methods like ultraviolet-visible spectroscopy, fourier transform infra-red spectroscopy, zeta potential measurement, dynamic light scattering and transmission electron microscopy. The effect of Pro-AuNPs on HEWL fibrillation was analyzed employing thioflavin T (ThT) and 8-Anilino-1-naphthalenesulfonic acid (ANS) assays. The kinetics of HEWL exhibited a typical sigmoidal nature of protein aggregation and was fitted to Boltzmann model. HEWL in the presence of bare gold nanoparticles (bAuNPs) exhibited similar aggregation kinetics as HEWL alone. However, HEWL fibrillation substantially reduced upon co-incubation with proline and Pro-AuNPs, and two slightly different intermediate species were formed with these two systems as predicted by CD spectroscopy. TEM images also supported the above observation displaying different morphological states of HEWL aggregates in the presence of proline and Pro-AuNPs. Using computational methods, the nature of interaction of HEWL and proline was found to be hydrogen bonding and hydrophobic interaction in multiple amyloidogenic regions. These interactions inhibited the formation of prefibrils (β-sheet rich intermediates) and also found to disintegrate fibrils. Furthermore, HEWL-Pro-AuNPs system resulted HEWL adsorption through hydrophobic patches, which blocked the intermolecular β-sheet formation. The present study successfully established Pro-AuNPs as a potential inhibitor of HEWL aggregation.

Keywords: Fibrillation; Functionalized gold nanoparticles; HEWL; Hydrophobic interaction; Proline.

MeSH terms

Animals
Gold / chemistry*
Metal Nanoparticles / administration & dosage*
Metal Nanoparticles / chemistry
Muramidase / chemistry*
Muramidase / drug effects
Proline / chemistry*
Protein Aggregates / drug effects*

Substances

Protein Aggregates
Gold
Proline
hen egg lysozyme
Muramidase