Extracellularly Detectable Electrochemical Signals of Living Cells Originate from Metabolic Reactions

Direct detection of cellular redox signals has shown immense potential as a novel living cell analysis tool. However, the origin of such signals remains unknown, which hinders the widespread use of electrochemical methods for cellular research. In this study, the authors found that intracellular metabolic pathways that generate adenosine triphosphate (ATP) are the main contributors to extracellularly detectable electrochemical signals. This is achieved through the detection of living cells (4,706 cells/chip, linearity: 0.985) at a linear range of 7,466-48,866. Based on this discovery, the authors demonstrated that the cellular signals detected by differential pulse voltammetry (DPV) can be rapidly amplified with a developed medium containing metabolic activator cocktails (MACs). The DPV approach combined with MAC treatment shows a remarkable performance to detect the effects of the anticancer drug CPI-613 on cervical cancer both at a low drug concentration (2 µm) and an extremely short treatment time (1 hour). Furthermore, the senescence of mesenchymal stem cells could also be sensitively quantified using the DPV+MAC method even at a low passage number (P6). Collectively, their findings unveiled the origin of redox signals in living cells, which has important implications for the characterization of various cellular functions and behaviors using electrochemical approaches.

 

Comments：

The authors of this study have found that intracellular metabolic pathways involved in generating adenosine triphosphate (ATP) are responsible for producing the electrochemical signals detected in living cells. This discovery provides important insights into the origins of redox signals in cells and opens up new possibilities for using electrochemical methods to study various cellular functions and behaviors.

The authors have demonstrated that the DPV approach combined with MAC treatment can effectively amplify cellular signals, enabling the sensitive detection of the effects of anticancer drugs on cancer cells and the quantification of senescence in mesenchymal stem cells. This approach shows promise as a powerful tool for studying cellular processes and developing new therapies.

Overall, this study highlights the potential of electrochemical methods for living cell analysis and provides important insights into the underlying mechanisms of cellular redox signaling.

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