Etezadi, DordanehWarner IV, John BlaineRuggeri, Francesco SDietler, GiovanniLashuel, Hilal AhmedAltug, Hatice2017-03-052017-03-052017-03-05201710.1038/lsa.2017.29https://infoscience.epfl.ch/handle/20.500.14299/134995Plasmonic 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.label-free biosensingnanoantennasplasmonicsprotein secondary structuresurface-enhanced infrared absorption spectroscopyNanoplasmonic mid-infrared biosensor for in vitro protein secondary structure detectiontext::journal::journal article::research article