Detection of amyloid fibrils in Parkinson’s disease using plasmonic chirality

Abstract

Amyloid fibrils, which are closely associated with various neurodegenerative diseases, are the final products in many protein aggregation pathways. The identification of fibrils at low concentration is, therefore, pivotal in disease diagnosis and development of therapeutic strategies. We report a methodology for the specific identification of amyloid fibrils using chiroptical effects in plasmonic nanoparticles. The formation of amyloid fibrils based on α-synuclein was probed using gold nanorods, which showed no apparent interaction with monomeric proteins but effective adsorption onto fibril structures via noncovalent interactions. The amyloid structure drives a helical nanorod arrangement, resulting in intense optical activity at the surface plasmon resonance wavelengths. This sensing technique was successfully applied to human brain homogenates of patients affected by Parkinson's disease, wherein protein fibrils related to the disease were identified through chiral signals from Au nanorods in the visible and near IR, whereas healthy brain samples did not exhibit any meaningful optical activity. The technique was additionally extended to the specific detection of infectious amyloids formed by prion proteins, thereby confirming the wide potential of the technique. The intense chiral response driven by strong dipolar coupling in helical Au nanorod arrangements allowed us to detect amyloid fibrils down to nanomolar concentrations.

Charge‐Induced Shifts in Chiral Surface Plasmon Modes in Gold Nanorod Assemblies

“…Although, the effect of charging on the extinction spectral features of plasmonic nanoparticles is well understood, it remains to be shown if electron charging may have a similar effect on the chiral surface plasmon modes of plasmonic nanoassemblies. With this question in mind, we have investigated the effect of chemical charging on the chiral LSPR modes generated when gold nanorods are assembled on a helical structure, templated by amyloid protein fibrils . Our results indeed confirm that chiral LSPR modes exhibit a significant wavelength shift in circular dichroism, upon charge injection into the nanorods within the helical assemblies.…”

“…Such small gold nanorods were synthesized following a seedless growth method, while α‐synuclein fibrils were generated by incubating the protein at high concentration on a shaker (details provided in the Experimental Section) . Addition of the nanofibrils into the Au nanorod colloidal dispersion resulted in gradual binding of nanorods on the fibril surface, as recently reported . The helical arrangement of Au nanorods on the chiral template results in a coupled longitudinal plasmon band at the near‐IR region of the extinction spectrum and a chiral plasmonic signal in the corresponding CD spectrum ( Figure a,b).…”

“…These spectral changes were accompanied by broadening of the LSPR band due to the presence of nanorod assemblies of different sizes and a significant polydispersity in interparticle distances. Details of the helical assembly of Au nanorods using protein fibrils as templates, as well as the origin of plasmonic CD, have been reported in detail, on the basis of cryo‐transmission electron microscopy (TEM) tomography and theoretical modeling, respectively . We further investigated the effects of charge injection through the stepwise addition of a solution of sodium borohydride, a strong reducing agent, into the dispersion of Au nanorod‐protein fibril nanocomposite structures.…”

“…The complementarity of specific functional groups in these biomolecules has been extensively used for the design and synthesis of a wide range of chiral nanoarchitectures that display circular dichroism (CD) signals at the LSPR wavelengths. This research has in turn generated a wide range of applications for chiral plasmons in the fields of chiral biodetection, enantioselective sensing, and catalysis . The basic principle behind most of these applications involves tuning chiral LSPR by varying the size and shape of the particles, through the controlled assembly of nanoparticles, by changing the interparticle distance, or by altering the dielectric constant of the surrounding medium.…”

Chiral Ag and Au Nanomaterials Based Optical Approaches for Analytical Applications

“…In the presence of sulfadimethoxine, the formation of nanoassemblies is suppressed, reducing the CD signal at 530 nm. Based on analyte inducing helical arrangement of Au nanorods, amyloid fibrils formed with α‐synuclein were detected by the CD signal of nanoassemblies . α‐Synuclein is a model recombinant protein for Parkinson's diseases.…”