title: Signature of protein unfolding in chemical exchange saturation transfer imaging.
abstract: Chemical exchange saturation transfer (CEST) allows the detection of metabolites of low concentration in tissue with nearly the sensitivity of MRI with water protons. With this spectroscopic imaging approach, several tissue-specific CEST effects have been observed in vivo. Some of these originate from exchanging sites of proteins, such as backbone amide protons, or from aliphatic protons within the hydrophobic protein core. In this work, we employed CEST experiments to detect global protein unfolding. Spectral evaluation revealed exchange- and NOE-mediated CEST effects that varied in a highly characteristic manner with protein unfolding tracked by fluorescence spectroscopy. We suggest the use of this comprehensive spectral signature for the detection of protein unfolding by CEST, as it relies on several spectral hallmarks. As proof of principle, we demonstrate that the presented signature is readily detectable using a whole-body MR tomograph (B0  = 7 T), not only in denatured aqueous protein solutions, but also in heat-shocked yeast cells. A CEST imaging contrast with the potential to detect global protein unfolding would be of particular interest regarding protein unfolding as a marker for stress, ageing, and disease.
authors.affiliation: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Goerke
authors.affiliation: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Zaiss
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kunz
authors.affiliation: Molecular Structure Analysis, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Karel D
authors.initials: KD
authors.lastname: Klika
authors.affiliation: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Windschuh
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Allianz, Heidelberg, Baden-Württemberg, Germany.|Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Mogk
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Allianz, Heidelberg, Baden-Württemberg, Germany.|Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Bukau
authors.affiliation: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ladd
authors.affiliation: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bachert
mesh_terms: D000465:Algorithms; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D051598:Whole Body Imaging / Q000379:methods
chemical_list: D011506:Proteins
keywords: BSA; CEST; NOE; chemical exchange; protein unfolding; yeast