Electrochemical Modulation of Carbon Monoxide‐Mediated Cell Signaling
Abstract
Despite the critical role played by carbon monoxide (CO) in physiological and pathological signaling events, current approaches to deliver this messenger molecule are often accompanied by off-target effects and offer limited control over release kinetics. To address these challenges, we develop an electrochemical approach that affords on-demand release of CO through reduction of carbon dioxide (CO₂) dissolved in the extracellular space. Electrocatalytic generation of CO by cobalt phthalocyanine molecular catalysts modulates signaling pathways mediated by a CO receptor soluble guanylyl cyclase. Furthermore, by tuning the applied voltage during electrocatalysis, we explore the effect of the CO release kinetics on CO-dependent neuronal signaling. Finally, we integrate components of our electrochemical platform into microscale fibers to produce CO in a spatially-restricted manner and to activate signaling cascades in the targeted cells. By offering on-demand local synthesis of CO, our approach may facilitate the studies of physiological processes affected by this gaseous molecular messenger.
Additional Information
© 2021 Wiley-VCH. Issue Online: 30 August 2021. Version of Record online: 11 August 2021. Accepted manuscript online: 15 July 2021. Manuscript received: 04 March 2021. We would like to thank T. Kitaguchi, and F. Zhang for the generous gifts of the plasmids and cell lines. The authors are also grateful to T. Khudiyev, S. Rao, and D. Rosenfeld for their technical advice on the experiments. This work was funded in part by the National Institutes of Health (NIH) BRAIN Initiative (5-R01-MH111872, 1-R01-NS115576), the National Institute of Neurological Disorders and Stroke (1-R01-NS115025), the National Science Foundation (NSF) Center for Neurotechnology (EEC-1028725), the Hock E. Tan and K. Lisa Yang Center for Autism Research, and the McGovern Institute for Brain Research. Work by K.M. and J.S.Z. was supported by the NSF under grant no. 1955628. This work made use of the MIT MRSEC Shared Experimental Facilities under award number DMR-14-19807 from the NSF. J.P. is a recipient of scholarship from the Kwanjeong Educational Foundation. A.S. is a recipient of the Lore Harp McGovern graduate student fellowship. The authors declare no conflict of interest.Attached Files
Supplemental Material - anie202103228-sup-0001-misc_information.pdf
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Additional details
- PMCID
- PMC8405587
- Eprint ID
- 114609
- Resolver ID
- CaltechAUTHORS:20220505-565109000
- 5-R01-MH111872
- NIH
- 1-R01-NS115576
- NIH
- 1-R01-NS115025
- NIH
- EEC-1028725
- NSF
- Hock E. Tan and K. Lisa Yang Center for Autism Research
- McGovern Institute for Brain Research
- CHE-1955628
- NSF
- DMR-1419807
- NSF
- Kwanjeong Educational Foundation
- Created
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2022-05-06Created from EPrint's datestamp field
- Updated
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2022-05-06Created from EPrint's last_modified field