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PreprintCC BYChemRxiv

An artificial macrophage reveals the impact of nitric oxide microenvironments on bacterial viability

  • Haiyuan Zou1,2
  • Ziqi Ding1,2
  • Sarah L. Weisflog3,4
  • Georgia R. Squyres3,4
  • Yifan Gao1,2
  • Yisi Chen1,2
  • Haley L. Marks5
  • Dianne K. Newman3,4,6
  • Chong Liu1,2,5
6 affiliations
  1. 1Department of Chemistry and Biochemistry
  2. 2University of California
  3. 3Division of Biology and Biological Engineering
  4. 4California Institute of Technology
  5. 5California NanoSystems Institute (CNSI), University of California
  6. 6Division of Geological and Planetary Sciences
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Abstract

Nitric oxide (NO) emitted from immune cells such as macrophages plays an important role in combating bacterial pathogens. Yet studying ephemeral NO-mediated interactions in real time, quantitatively, and at the single-cell level has been technically challenging. Here we present an “artificial macrophage”: a live-cell imaging platform that overcomes these challenges by leveraging electrochemistry to generate micropatterned NO gradients at infection-relevant concentrations. We achieve this capability using a biocompatible electrocatalyst that selectively transforms ammonia into NO in biological media. Using Pseudomonas aeruginosa as a model NO-responsive pathogen, we show that the NO microenvironment, influenced by both extracellular NO concentrations and NO gradients experienced by cells, underpins NO’s bactericidal efficacy for individual surface-associated cells. Our results highlight that considering NO’s reaction-diffusion, rather than just its local concentration, is key to understanding how the extracellular microenvironment affects single-cell bacterial viability. Spatiotemporal control of NO microenvironments using our live-cell imaging platform will advance studies of diverse cell types that regularly encounter NO.

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Cite

BibTeXRIS
BibTeX
@misc{zou2026artificial,
  title = {{An artificial macrophage reveals the impact of nitric oxide microenvironments on bacterial viability}},
  author = {Haiyuan Zou and Ziqi Ding and Sarah L. Weisflog and Georgia R. Squyres and Yifan Gao and Yisi Chen and Haley L. Marks and Dianne K. Newman and Chong Liu},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15010647/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010647/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - An artificial macrophage reveals the impact of nitric oxide microenvironments on bacterial viability
AU  - Haiyuan Zou
AU  - Ziqi Ding
AU  - Sarah L. Weisflog
AU  - Georgia R. Squyres
AU  - Yifan Gao
AU  - Yisi Chen
AU  - Haley L. Marks
AU  - Dianne K. Newman
AU  - Chong Liu
PY  - 2026
DA  - 2026/10/19
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15010647/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010647/v1
AB  - Nitric oxide (NO) emitted from immune cells such as macrophages plays an important role in combating bacterial pathogens. Yet studying ephemeral NO-mediated interactions in real time, quantitatively, and at the single-cell level has been technically challenging. Here we present an “artificial macrophage”: a live-cell imaging platform that overcomes these challenges by leveraging electrochemistry to generate micropatterned NO gradients at infection-relevant concentrations. We achieve this capability using a biocompatible electrocatalyst that selectively transforms ammonia into NO in biological media. Using Pseudomonas aeruginosa as a model NO-responsive pathogen, we show that the NO microenvironment, influenced by both extracellular NO concentrations and NO gradients experienced by cells, underpins NO’s bactericidal efficacy for individual surface-associated cells. Our results highlight that considering NO’s reaction-diffusion, rather than just its local concentration, is key to understanding how the extracellular microenvironment affects single-cell bacterial viability. Spatiotemporal control of NO microenvironments using our live-cell imaging platform will advance studies of diverse cell types that regularly encounter NO.
ER  -