Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging
Neurotransmitter-sensitive contrast agents for magnetic resonance imaging (MRI) have recently been used for mapping signaling dynamics in live animal brains, but paramagnetic sensors for T1-weighted MRI are usually effective only at micromolar concentrations that themselves perturb neurochemistry. H...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/125916 |
| _version_ | 1826188843610537984 |
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| author | Hsieh, Vivian Okada, Satoshi Wei, He Garcia Alvarez, Isabel Barandov, Ali Alvarado, Santiago Recuenco Ohlendorf, Robert Fan, Jingxuan Ortega, Athena Jasanoff, Alan Pradip |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Hsieh, Vivian Okada, Satoshi Wei, He Garcia Alvarez, Isabel Barandov, Ali Alvarado, Santiago Recuenco Ohlendorf, Robert Fan, Jingxuan Ortega, Athena Jasanoff, Alan Pradip |
| author_sort | Hsieh, Vivian |
| collection | MIT |
| description | Neurotransmitter-sensitive contrast agents for magnetic resonance imaging (MRI) have recently been used for mapping signaling dynamics in live animal brains, but paramagnetic sensors for T1-weighted MRI are usually effective only at micromolar concentrations that themselves perturb neurochemistry. Here we present an alternative molecular architecture for detecting neurotransmitters, using superparamagnetic iron oxide nanoparticles conjugated to tethered neurotransmitter analogs and engineered neurotransmitter binding proteins. Interactions between the nanoparticle conjugates result in clustering that is reversibly disrupted in the presence of neurotransmitter analytes, thus altering T2-weighted MRI signals. We demonstrate this principle using tethered dopamine and serotonin analogs, together with proteins selected for their ability to competitively bind either the analogs or the neurotransmitters themselves. Corresponding sensors for dopamine and serotonin exhibit target-selective relaxivity changes of up to 20%, while also operating below endogenous neurotransmitter concentrations. Semisynthetic magnetic particle sensors thus represent a promising path for minimally perturbative studies of neurochemical analytes. |
| first_indexed | 2024-09-23T08:05:34Z |
| format | Article |
| id | mit-1721.1/125916 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:05:34Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1259162022-09-23T10:52:06Z Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging Hsieh, Vivian Okada, Satoshi Wei, He Garcia Alvarez, Isabel Barandov, Ali Alvarado, Santiago Recuenco Ohlendorf, Robert Fan, Jingxuan Ortega, Athena Jasanoff, Alan Pradip Massachusetts Institute of Technology. Department of Biological Engineering Neurotransmitter-sensitive contrast agents for magnetic resonance imaging (MRI) have recently been used for mapping signaling dynamics in live animal brains, but paramagnetic sensors for T1-weighted MRI are usually effective only at micromolar concentrations that themselves perturb neurochemistry. Here we present an alternative molecular architecture for detecting neurotransmitters, using superparamagnetic iron oxide nanoparticles conjugated to tethered neurotransmitter analogs and engineered neurotransmitter binding proteins. Interactions between the nanoparticle conjugates result in clustering that is reversibly disrupted in the presence of neurotransmitter analytes, thus altering T2-weighted MRI signals. We demonstrate this principle using tethered dopamine and serotonin analogs, together with proteins selected for their ability to competitively bind either the analogs or the neurotransmitters themselves. Corresponding sensors for dopamine and serotonin exhibit target-selective relaxivity changes of up to 20%, while also operating below endogenous neurotransmitter concentrations. Semisynthetic magnetic particle sensors thus represent a promising path for minimally perturbative studies of neurochemical analytes. National Institutes of Health (Grant R01-DA038642) National Institutes of Health (Grant R01-DA02899) 2020-06-22T17:44:20Z 2020-06-22T17:44:20Z 2019-09 2019-08 2020-06-22T12:12:03Z Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 https://hdl.handle.net/1721.1/125916 Hsieh, Vivian et al. "Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging." Journal of the American Chemical Society 141, 40 (September 2019): 15751–15754 © 2019 American Chemical Society en http://dx.doi.org/10.1021/jacs.9b08744 Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf application/pdf American Chemical Society (ACS) Prof. Jasanoff via Howard Silver |
| spellingShingle | Hsieh, Vivian Okada, Satoshi Wei, He Garcia Alvarez, Isabel Barandov, Ali Alvarado, Santiago Recuenco Ohlendorf, Robert Fan, Jingxuan Ortega, Athena Jasanoff, Alan Pradip Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging |
| title | Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging |
| title_full | Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging |
| title_fullStr | Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging |
| title_full_unstemmed | Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging |
| title_short | Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging |
| title_sort | neurotransmitter responsive nanosensors for t2 weighted magnetic resonance imaging |
| url | https://hdl.handle.net/1721.1/125916 |
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