Electrochemical Modulation of Carbon Monoxide‐Mediated Cell Signaling

• Published in: Angewandte Chemie 2021-09, Vol.133 (37), p.20488-20493
• Main Authors: Park, Jimin, Zeng, Joy S., Sahasrabudhe, Atharva, Jin, Kyoungsuk, Fink, Yoel, Manthiram, Karthish, Anikeeva, Polina
• Format: Article
• Language: English
• Subjects: Carbon dioxide; Carbon monoxide; Catalysts; Cell signaling; Chemistry; Cobalt; Electrochemistry; fiber drawing; Fibers; Guanylate cyclase; Kinetics; Physiology; receptors; Signaling
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202103228

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. An electrochemical strategy to locally synthesize carbon monoxide (CO), a gaseous messenger molecule, with tunable kinetics is devised. By integrating this strategy with fiber‐based fabrication, diverse CO‐dependent signaling pathways in genetically engineered cells or neurons can be modulated at the microscale.