2024/05/22 by Narayanankutty, Krishnadev, Pereiro-Morejon, José Antonio, Ferrero-Fernández, Arián +7 · 2 citations
#Biological Physics (physics.bio-ph) #Cell Behavior (q-bio.CB) #FOS: Biological sciences #FOS: Physical sciences #Statistical Mechanics (cond-mat.stat-mech)
paper · doi:10.48550/arxiv.2405.13424
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.