ao8b03169_si_001.pdf (248.6 kB)
Effect of Silica Nanoparticles on the Amyloid Fibrillation of Lysozyme
journal contribution
posted on 2019-01-11, 17:53 authored by Mouli Konar, Ashwin Mathew, Swagata DasguptaProtein
fibrils are regarded as undesired products as these are
associated with numerous neuro- and non-neurodegenerative disorders.
Increasing evidence suggests that the mechanism of fibrillation involves
the formation of various oligomeric intermediates, which are known
to be more toxic than mature fibrils. Here, we report the impact of
synthesized silica nanoparticles (SiNPs) of diameters ∼52 nm
on the aggregation behavior of hen egg white lysozyme (HEWL) under
heat and acidic conditions. Congo red as well as ThT binding assays
and AFM imaging studies indicate that SiNPs trigger the amyloid formation
of HEWL in a dose-dependent manner. ThT kinetic studies and FTIR studies
suggest that the fibrillation kinetics does not involve the formation
of toxic oligomeric intermediates at higher concentrations of SiNPs.
By measuring fluorescence lifetime values of the bound ThT, SiNP-induced
fibrillation of HEWL can easily be realized. CD spectroscopic studies
indicate that native HEWL becomes unfolded upon incubation under the
experimental conditions and is rapidly converted into the β-sheet-rich
fibrillar aggregates in the presence of SiNPs with increasing concentrations.
It has been further revealed that fibrillar aggregates formed at higher
concentrations of SiNPs preferably adopt an antiparallel β-sheet
configuration. The enhanced fibrillation in the presence of SiNPs
is likely because of preferential adsorption of the non-amyloidogenic
regions of HEWL, resulting in the exposure of the aggregation-prone
regions of HEWL toward the solvent. The study will provide deeper
insights into the evolution of oligomer-free fibrillation that can
be useful to demonstrate the underlying mechanism of amyloid fibrillation.