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A protein-based biosensor for detecting calcium by magnetic resonance imaging

Harun F. Ozbakir, Austin D.C. Miller, Kiara B. Fishman, André F. Martins, Tod E. Kippin, View ORCID ProfileArnab Mukherjee
doi: https://doi.org/10.1101/2021.02.04.429691
Harun F. Ozbakir
1Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA
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Austin D.C. Miller
2Biomolecular Science and Engineering, University of California, Santa Barbara, CA 93106, USA
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Kiara B. Fishman
3Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
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André F. Martins
4Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen 72076, Germany
5Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen 72076, Germany
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Tod E. Kippin
6Department of Psychological and Bran Sciences, University of California, Santa Barbara, CA 93106, USA
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Arnab Mukherjee
1Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA
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  • ORCID record for Arnab Mukherjee
  • For correspondence: arnabm@ucsb.edu
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ABSTRACT

Calcium-responsive contrast agents for magnetic resonance imaging (MRI) offer an attractive approach to noninvasively image neural activity with wide coverage in deep brain regions. However, current MRI sensors for calcium are based on synthetic architectures fundamentally incompatible with genetic technologies for in vivo delivery and targeting. Here, we present a protein-based MRI sensor for calcium, derived from a calcium-binding protein known as calprotectin. Calcium-binding causes calprotectin to sequester manganese. We demonstrate that this mechanism allows calprotectin to alter T1 and T2 weighted contrast in response to biologically relevant calcium concentrations. Corresponding changes in relaxation times are comparable to synthetic calcium sensors and exceed those of previous protein-based MRI sensors for other neurochemical targets. The biological applicability of calprotectin was established by detecting calcium in lysates prepared from a neuronal cell line. Calprotectin thus represents a promising path towards imaging neural activity by combining the benefits of MRI and protein sensors.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 04, 2021.
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A protein-based biosensor for detecting calcium by magnetic resonance imaging
Harun F. Ozbakir, Austin D.C. Miller, Kiara B. Fishman, André F. Martins, Tod E. Kippin, Arnab Mukherjee
bioRxiv 2021.02.04.429691; doi: https://doi.org/10.1101/2021.02.04.429691
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A protein-based biosensor for detecting calcium by magnetic resonance imaging
Harun F. Ozbakir, Austin D.C. Miller, Kiara B. Fishman, André F. Martins, Tod E. Kippin, Arnab Mukherjee
bioRxiv 2021.02.04.429691; doi: https://doi.org/10.1101/2021.02.04.429691

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