Real-time protein aggregation monitoring with a Bloch surface wave-based approach

Abstract

The misfolding and aggregation of amyloid proteins has been associated with incurable diseases such as Alzheimer's or Parkinson's disease. In the specific case of Alzheimer's disease, recent studies have shown that cell toxicity is caused by soluble oligomeric forms of aggregates appearing in the early stages of aggregation, rather than by insoluble fibrils. Research on new strategies of diagnosis is imperative to detect the disease prior to the onset of clinical symptoms. Here, we propose the use of an optical method for protein aggregation dynamic studies using a Bloch surface wave based approach. A one dimension photonic crystal made of a periodic stack of silicon oxide and silicon nitride layers is used to excite a Bloch surface wave, which is sensitive to variation of the refractive index of an aqueous solution. The aim is to detect the early dynamic events of protein aggregation and fibrillogenesis of the amyloid-beta peptide Aβ42, which plays a central role in the onset of the Alzheimer's disease. The detection principle relies on the refractive index changes caused by the depletion of the Aβ42 monomer concentration during oligomerization and fibrillization. We demonstrate the efficacy of the Bloch surface wave approach by monitoring in real-time the first crucial steps of Aβ42 oligomerization.

Real-Time Study of the Adsorption and Grafting Process of Biomolecules by Means of Bloch Surface Wave Biosensors

“…19 The strongly confined electromagnetic field associated to the BSW can be used as a probe to detect biomolecular binding events in a very thin layer close to the surface (about 100 nm). Recently several groups reported on the application of BSW, with several different optical sensing schemes, to the field of cancer biomarkers detection 17,20 and to the study of the conformational changes of proteins, 21 which is relevant for the further understanding of the biological performance of biomaterials. Compared to the surface enhanced infrared absorption (SEIRA) 22 and surface plasmon resonance (SPR) 23 spectroscopy techniques, which exploit the excitation of surface plasmon polaritons (SPP), the main advantages of BSW are in that their dispersion can be almost arbitrarily tuned in wavelength, momentum and polarization by changing the 1DPC materials and geometry.…”