Does Surface Chirality of Gold Nanoparticles Affect Fibrillation of HSA?

Abstract

In order to demonstrate the influence of the surface chirality of the nanoparticles on amyloid fibrillation, the inhibiting effectiveness of the chiral gold nanoparticles, synthesized using the two enantiomeric forms (i.e., d- and l-) of glutamic acid, toward the fibrillation of human serum albumin (HSA) has been investigated. Here the enantiomers of glutamic acid are used as both reducing and stabilizing/capping agents. It is found that the surface chirality is the only major difference between the d-glutamic acid mediated gold (DGAu) and l-glutamic acid mediated gold (LGAu) nanoparticles. The fibrillation process has been monitored using various biophysical techniques, e.g., turbidity assay, Thioflavin T fluorescence kinetics, Congo red binding study, circular dichroism spectroscopy, fluorescence microscopy, and transmission electron microscopy. The experimental results illustrate that DGAu is more effective in inhibiting the formation of HSA fibrils than LGAu. Furthermore, the differential inhibiting effect of DGAu and LGAu toward HSA fibrillation has been described on the basis of the dissimilar interaction behavior of the nanoparticles with the HSA molecules, as revealed by the Trp fluorescence quenching, and the isothermal titration calorimetry. It is suggested that the surface chirality of the gold nanoparticles strongly influences the protein adsorption dynamics including the modes of orientation of adsorbed HSA molecules, causing the inhibition of fibrillation to different extents.

Polyphenol capping on a gold nanosurface modulates human serum albumin fibrillation

“…15 AuNPs have also exhibited tremendous potency in the management of oxidatively stressed conditions through quenching of free radical species. 16,17 AuNPs have been strategically explored as one platform for studying the influence of nanosurface charge, 18 surface chirality, 19 shape and size 20 on protein fibrillation.…”

Nanochaperone‐Based Strategies to Control Protein Aggregation Linked to Conformational Diseases

“…Surface functionalization with peptides : Tryptophan, tyrosine [83] or glutamic acid [84] as NP coatings have allowed fibril inhibition and even disaggregation. Glutamic acid‐functionalization revealed that chirality affects amyloid fibrillation; AuNPs bearing the d ‐enantiomer were more efficient with human serum albumin (HSA) [84] .…”

“…[80] Inhibitory activities of bare (citrate) AuNPs were also observed with Ab [81] and insulin; [82] fibrillation was significantly delayed and the final aggregate structure,s hape,a nd density were altered. vi) Surface functionalization with peptides: Tr yptophan, tyrosine [83] or glutamic acid [84] as NP coatings have allowed fibril inhibition and even disaggregation. Glutamic acid-functionalization revealed that chirality affects amyloid fibrillation;A uNPs bearing the d-enantiomer were more efficient with human serum albumin (HSA).…”

Nanochaperone‐Based Strategies to Control Protein Aggregation Linked to Conformational Diseases

“…Glutamic acid-functionalization revealed that chirality affects amyloid fibrillation;A uNPs bearing the d-enantiomer were more efficient with human serum albumin (HSA). [84] b-sheet breaker peptides,w hich recognize the hydrophobic domain of amyloidogenic proteins and interfere with b-structured aggregates,h ave also been used to increase the adhesion of Ab to NPs and enhance inhibition over fibrillation. LV FFARK-functionalized NPs restricted Ab42 conformational changes,redirected its aggregation into unstructured, off-pathway aggregates and reduced Ab toxicity.…”