Monolayer Sensitivity Enables a 2D IR Spectroscopic Immuno-biosensor for Studying Protein Structures: Application to Amyloid Polymorphs

Immunosensors use antibodies to detect and quantify biomarkers of disease, though the sensors often lack structural information. We create a surface-sensitive two-dimensional infrared (2D IR) spectroscopic immunosensor for studying protein structures. We tether antibodies to a plasmonic surface, flo...

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Bibliographic Details
Published in:The journal of physical chemistry letters 2019-07, Vol.10 (14), p.3836-3842
Main Authors: Ostrander, Joshua S, Lomont, Justin P, Rich, Kacie L, Saraswat, Vivek, Feingold, Benjamin R, Petti, Megan K, Birdsall, Erin R, Arnold, Michael S, Zanni, Martin T
Format: Article
Language:English
Subjects:
Amyloid - chemistry
Biosensing Techniques
Chemistry
Humans
Islet Amyloid Polypeptide - chemistry
Materials Science
Physics
Protein Conformation
Science & Technology - Other Topics
Spectrophotometry, Infrared
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Summary:Immunosensors use antibodies to detect and quantify biomarkers of disease, though the sensors often lack structural information. We create a surface-sensitive two-dimensional infrared (2D IR) spectroscopic immunosensor for studying protein structures. We tether antibodies to a plasmonic surface, flow over a solution of amyloid proteins, and measure the 2D IR spectra. The 2D IR spectra provide a global assessment of antigen structure, and isotopically labeled proteins give residue-specific structural information. We report the 2D IR spectra of fibrils and monomers using a polyclonal antibody that targets human islet amyloid polypeptide (hIAPP). We observe two fibrillar polymorphs differing in their structure at the G24 residue, which supports the hypothesis that hIAPP polymorphs form from a common oligomeric intermediate. This work provides insight into the structure of hIAPP, establishes a new method for studying protein structures using 2D IR spectroscopy, and creates a spectroscopic immunoassay applicable for studying a wide range of biomarkers.
ISSN:1948-7185
1948-7185
DOI:10.1021/acs.jpclett.9b01267