Nanoelectrochemical quantification of single-cell metabolism
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Nanoelectrochemical quantification of single-cell metabolism Hadley K. McCormick 1 & Jeffrey E. Dick 1,2 Received: 29 June 2020 / Revised: 10 August 2020 / Accepted: 18 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract At the most fundamental level, the behavior of tissue is governed by the activity of its single cells. A detailed examination of single-cell biology is necessary in order to gain a deeper understanding of disease progression. While single-cell genomics and transcriptomics are mature due to robust amplification strategies, the metabolome is difficult to quantify. Nanoelectrochemical techniques stand poised to quantify single-cell metabolism as a result of the fabrication of nanoelectrodes, which allow one to make intracellular electrochemical measurements. This article is concerned with intracellular nanoelectrochemistry, focusing on the sensitive and selective quantification of various metabolites within a single, living cell. We will review the strong literature behind this field, discuss the potential deleterious effects of passing charge inside cells, and provide future outlooks for this promising avenue of inquiry. We also present a mathematical relationship based on Faraday’s Law and bulk electrolysis theory to examine the consumption of analyte within a cell due to passing charge at the nanotip. Keywords Nanoelectrochemistry . Single-cell biology . Metabolism . Electrolysis
Introduction To completely understand the extraordinary complexity of tissue, an in-depth analysis of activity at the single-cell level is required. The study of single-cell behavior, both isolated and within a population, promises to elucidate heterogeneities that cannot be observed when measuring over a large number of cells. Considering many diseases, including cancer, begin with a single cell, these studies are worth pursuit. The progression of disease can be marked by a change in the concentration of certain cellular metabolites, indicating their quantification is important. For instance, overproduction of reactive oxygen species (ROS) or reactive nitrogen species (RNS) within the cell has been shown to coincide with cancer [1–3], and a high concentration of hydroxyl radicals (•OH) within the cell can signal Alzheimer’s disease [4, 5]. In addition, a low level of dopamine in the midbrain can be a marker for Parkinson’s disease [6–8]. Thus, measuring the * Jeffrey E. Dick [email protected] 1
Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2
Lineberger Comprehensive Cancer Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
concentration of cellular metabolites can be useful in identifying the initial stages of disease within a single cell before the condition develops and begins to affect tissue function. While it is not feasible for nanoelectrodes to be used to monitor every cell in a human body, nanoelectrodes could possibly be used in the future to sense the early si
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