Picomolar Biosensing and Conformational Analysis Using Artificial Bidomain Proteins and Terbium-to-Quantum Dot Förster Resonance Energy TransferClick to copy article linkArticle link copied!
- Corentin LégerCorentin LégerUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, FranceMore by Corentin Léger
- Akram Yahia-AmmarAkram Yahia-AmmarUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, FranceMore by Akram Yahia-Ammar
- Kimihiro SusumuKimihiro SusumuOptical Sciences Division, Code 5600, U.S. Naval Research Laboratory, Washington, D.C. 20375, United StatesKeyW Corporation, Hanover, Maryland 21076, United StatesMore by Kimihiro Susumu
- Igor L. MedintzIgor L. MedintzCenter for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, D.C. 20375, United StatesMore by Igor L. Medintz
- Agathe Urvoas*Agathe Urvoas*Email: [email protected]Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, FranceMore by Agathe Urvoas
- Marie Valerio-Lepiniec*Marie Valerio-Lepiniec*Email: [email protected]Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, FranceMore by Marie Valerio-Lepiniec
- Philippe Minard*Philippe Minard*Email: [email protected]Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, FranceMore by Philippe Minard
- Niko Hildebrandt*Niko Hildebrandt*Email: [email protected]Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, FrancenanoFRET.com, Laboratoire COBRA (Chimie Organique, Bioorganique, Réactivité et Analyse), Université de Rouen Normandie, CNRS, INSA, 76821 Mont-Saint-Aignan, FranceMore by Niko Hildebrandt
Abstract

Although antibodies remain a primary recognition element in all forms of biosensing, functional limitations arising from their size, stability, and structure have motivated the development and production of many different artificial scaffold proteins for biological recognition. However, implementing such artificial binders into functional high-performance biosensors remains a challenging task. Here, we present the design and application of Förster resonance energy transfer (FRET) nanoprobes comprising small artificial proteins (αRep bidomains) labeled with a Tb complex (Tb) donor on the C-terminus and a semiconductor quantum dot (QD) acceptor on the N-terminus. Specific binding of one or two protein targets to the αReps induced a conformational change that could be detected by time-resolved Tb-to-QD FRET. These single-probe FRET switches were used in a separation-free solution-phase assay to quantify different protein targets at sub-nanomolar concentrations and to measure the conformational changes with sub-nanometer resolution. Probing ligand–receptor binding under physiological conditions at very low concentrations in solution is a special feature of FRET that can be efficiently combined with other structural characterization methods to develop, understand, and optimize artificial biosensors. Our results suggest that the αRep FRET nanoprobes have a strong potential for their application in advanced diagnostics and intracellular live-cell imaging of ligand–receptor interactions.
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