Metabolic coordination and phase transitions in spatially distributed multi-cellular systems
arXiv:2405.13424 · doi:10.1038/s42005-025-02133-x
Abstract
During overflow metabolism, cells excrete glycolytic byproducts when growing under aerobic conditions in a seemingly wasteful fashion. While potentially advantageous for microbes with finite oxidative capacity, its role in higher organisms is harder to assess. Recent single-cell experiments suggest overflow metabolism arises due to imbalances in inter-cellular exchange networks. We quantitatively characterize this scenario by integrating spatial metabolic modeling with tools from statistical physics and experimental single-cell flux data. Our results provide a theoretical demonstration of how diffusion-limited exchanges shape the space of accessible multi-cellular metabolic states. Specifically, a phase transition from a balanced network of exchanges to an unbalanced, overflow regime occurs as mean glucose and oxygen uptake rates vary. Heterogeneous single-cell metabolic phenotypes occur near this transition. Time-resolved tumor-stroma co-culture data support the idea that overflow metabolism stems from failure of inter-cellular metabolic coordination. In summary, environmental control is an emergent multi-cellular property, rather than a cell-autonomous effect.
Main (20 pages) + Supplementary information (15 pages). Published in Communications Physics 8, 205 (2025) (DOI: 10.1038/s42005-025-02133-x)
References in corpus (7)
- Computation Of Microbial Ecosystems in Time and Space (COMETS): An open source collaborative platform for modeling ecosystems metabolism
- Fluorescent nano- and microparticles for sensing cellular microenvironment: past, present and future applications
- Characterizing steady states of genome-scale metabolic networks in continuous cell cultures
- Probing the pH microenvironment of mesenchymal stromal cell cultures on additive-manufactured scaffolds
- Quantitative constraint-based computational model of tumor-to-stroma coupling via lactate shuttle
- Highly Sensitive Ratiometric Fluorescent Fiber Matrixes for Oxygen Sensing with Micrometer-Spatial Resolution
- Path-integral solution of MacArthur's resource-competition model for large ecosystems with random species-resources couplings