RT Journal Article T1 Stabilization of Non-Native Folds and Programmable Protein Gelation in Compositionally Designed Deep Eutectic Solvents A1 Sánchez Fernández, Adrián A1 Poon, Jia-Fei A1 Leung, Anna Elizabeth A1 Prévost, Sylvain François A1 Dicko, Cedric K1 Deep eutectic solvent K1 Protein conformation K1 Folding intermediates K1 Supramolecular entanglement K1 Protein eutectogel AB Proteins are adjustable units from which biomaterials with designed properties can be developed. However, non-native folded states with controlled topologies are hardly accessible in aqueous environments, limiting their prospects as building blocks. Here, we demonstrate the ability of a series of anhydrous deep eutectic solvents (DESs) to precisely control the conformational landscape of proteins. We reveal that systematic variations in the chemical composition of binary and ternary DESs dictate the stabilization of a wide range of conformations, that is, compact globular folds, intermediate folding states, or unfolded chains, as well as controlling their collective behavior. Besides, different conformational states can be visited by simply adjusting the composition of ternary DESs, allowing for the refolding of unfolded states and vice versa. Notably, we show that these intermediates can trigger the formation of supramolecular gels, also known as eutectogels, where their mechanical properties correlate to the folding state of the protein. Given the inherent vulnerability of proteins outside the native fold in aqueous environments, our findings highlight DESs as tailorable solvents capable of stabilizing various non-native conformations on demand through solvent design PB ACS SN 1936-0851 YR 2024 FD 2024-07-01 LK http://hdl.handle.net/10347/34948 UL http://hdl.handle.net/10347/34948 LA eng NO ACS Nano 2024, 18, 28, 18314–18326 NO We are thankful for the financial support of Spanish grants PID2022-141673OA-I00 funded by MCIN/AEI and by “ERDF A way of making Europe”. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 101063372. J.-F.P acknowledges Tillväxtverket – Swedish Agency for Economic and Regional Growth (grant no. 20205513) for the financial support. The authors thank the Institute Laue-Langevin for the awarded beamtime. This work was carried out using choline (trimethyl-d9) acetate-d3 as a result of proposal 440978 at the European Spallation Source ERIC. The persistent identified for the sample is DOI: 10.5281/zenodo.10068938. This work benefited from the use of the SasView application, originally developed under NSF award DMR-0520547. SasView contains code developed with funding from the European Union’s Horizon 2020 research and innovation programme under the SINE2020 project, grant agreement no. 654000. The authors express their gratitude to Prof. Ana Soto and Dr. Carlos A. Pena for the valuable assistance with density and viscosity analyses and to Dr. Giulia Zampini and Dr. Arcadio Guerra-Fandiño for their support in conducting excited-state fluorescence measurements DS Minerva RD 30 abr 2026