Electrochemically generated microenvironments of oxygen and reactive oxygen/nitrogen species in extracellular medium

University Of California Los Angeles, Los Angeles CA

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Abstract

Project Summary The spatiotemporal heterogeneity of extracellular environments is ubiquitously critical for the metabolism and physiology of prokaryotic and eukaryotic organisms. Yet our tools for the spatiotemporal creation and/or perturbation of microenvironments are currently limited. Controlling microenvironments in the extracellular medium is particularly challenging for unstable reactive species, such as reactive oxygen and nitrogen species (ROS and RNS), because the classic method of dosing ROS and RNS donors cannot provide a constant ROS/RNS concentration and is unable to develop spatial gradients/microenvironments at microscopic scale to fully mimic many in vivo conditions. Such difficulties of designing and programming spatiotemporal microenvironments impedes more in-depth understandings towards single-cell microbial metabolism/physiology as well as subcellular metabolic responses for eukaryotic systems. We envision that selective biocompatible electrochemistry are capable of addressing these challenges by generating or consuming biologically important species, such as O2 and ROS/RNS, directly in the extracellular medium. We hypothesize that selective biocompatible electrochemistry will create spatiotemporal O2 and ROS/RNS profiles otherwise difficult to achieve and advance our understanding of biological systems in a spatially and temporally well-defined manner. This proposal outlines our overarching approach to develop and deploy programmable spatiotemporal O2 and ROS/RNS microenvironments primarily for platforms compatible with fluorescence microscopy. To achieve our vision, we will understand organisms’ metabolic responses towards electrochemically active materials in biological medium. We will design selective electrochemical transformations while keeping the electrochemistry biocompatible. Furthermore, we will develop O2 and ROS/RNS microenvironments generated by electrochemistry and deploy such microenvironments to study single-cell metabolism/physiology of infectious bacteria as well as metabolic responses at subcellular level. The proposed research adopts a transdisciplinary approach integrating inorganic/materials chemistry, electrochemistry, metabolomics, microbiology, cell biology and wearable electronics, thanks to the multidisciplinary expertise of the PI and collaborators’ team. Successful development from the proposed research will enrich our tools of perturbing extracellular microenvironments under conditions compatible with characterization platforms such as fluorescence microscopy. It will enable researchers to understand biomedical systems with higher spatiotemporal precision.