Reconstructing physiological oxygen gradients reveals the role of hypoxia in colon epithelial organization.
| Publication Type | Preprint |
| Authors | Yu J, Chen C, Rodriguez F, Yee G, Zeng I, Yang K, Benitez E, Ganesh K, Manalis S |
| Journal | bioRxiv |
| Date Published | 12/19/2025 |
| ISSN | 2692-8205 |
| Abstract | Oxygen gradients organize tissue architecture and metabolism 1,2 , yet their precise spatial profiles and mechanistic roles remain poorly understood because both in vivo measurement and in vitro control are technically challenging 3,4 . Here, we quantify the oxygen landscape of the mammalian intestine using microscale sensors, revealing a steep luminal-basal gradient of approximately 10-60 µM mm - 1 that collapses under antibiotic perturbation. We then recreate this physiological range ex vivo with a submerged chemostat microfluidic platform that fixes the oxygen boundary condition by coupling an oxygen-permeable PDMS chip to an external scavenger reservoir and integrating embedded optical sensors for real-time readout. This architecture suppresses ambient oxygen ingress and sustains programmable gradients of 10-20 µM mm - 1 across three-dimensional colorectal cancer organoid cultures while remaining compatible with live imaging and endpoint retrieval. The platform bridges quantitative in vivo oxygen mapping with controlled ex vivo modeling, establishing a generalizable approach to interrogate how spatial oxygen dynamics govern epithelial organization and disease progression. |
| DOI | 10.64898/2025.12.16.694730 |
| PubMed ID | 41446248 |
| PubMed Central ID | PMC12724557 |