Year: 2017
Type: article
Abstract: Plasmonic nanoantennas offer new applications in mid-infrared (mid-IR) absorption spectroscopy with ultrasensitive detection of structural signatures of biomolecules, such as proteins, due to their strong resonant near-fields. The amide I fingerprint of a protein contains conformational information that is greatly important for understanding its function in health and disease. Here, we introduce a non-invasive, label-free mid-IR nanoantenna-array sensor for secondary structure identification of nanometer-thin protein layers in aqueous solution by resolving the content of plasmonically enhanced amide I signatures. We successfully detect random coil to cross β-sheet conformational changes associated with α-synuclein protein aggregation, a detrimental process in many neurodegenerative disorders. Notably, our experimental results demonstrate high conformational sensitivity by differentiating subtle secondary-structural variations in a native β-sheet protein monolayer from those of cross β-sheets, which are characteristic of pathological aggregates. Our nanoplasmonic biosensor is a highly promising and versatile tool for in vitro structural analysis of thin protein layers. Using arrays of gold nanorods to probe thin protein films can reveal the precise vibrational fingerprints of 3D helices and sheets. The higher-order geometric conformations of proteins play crucial roles in diseases such as Alzheimer’s, but observing these structures in their native states is challenging. A sensor developed by Dordaneh Etezadi and colleagues from EPFL in Switzerland can now spot subtle secondary structural differences between proteins in physiological conditions by using non-invasive plasmonic fields. Samples such as α-synuclein proteins associated with neurodegenerative disorders were deposited onto a gold antenna array fabricated to maximize coupling of light with the specific vibrations of amide groups involved in secondary bonding in physiological conditions. Analytical treatment of the plasmonic spectra uncovered distinct signatures of conformational changes from random coils to cross β-sheets, which cause α-synuclein to aggregate and disrupt normal neuron functions.
Source: Light Science & Applications
DOI: 10.1038/lsa.2017.29
Language: English
Subfield: Atomic and Molecular Physics, and Optics
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,190
Awards: Ultrasensitive chiral detection by signal-reversing cavity polarimetry: applications to in-situ proteomics, single-molecule chirality, HPLC analysis, medical diagnostics, and atmospheric studies, G434337789, Correlating biophysical properties of amyloid aggregates in vitro and in vivo by AFM-based infrared nanospectroscopy, High-throughput vibrational fingerprinting by nanoplasmonics for disease biology, Bringing Together Nanoscale and Bulk Approaches for the Biophysical Characterization of Protein Aggregation, Single Molecule AFM Study of Amyloid Fibrils, Polysaccharides and Fibrous Supramolecular Complexes, Towards deciphering the role of N-terminal post-translational modifications in regulating the function of Huntingtin (Htt) in health and disease
OpenAlex ID: W2593718978