Cellular gradient flow structure linking single-cell-level rules and population-level dynamics

Abstract

In multicellular systems, single-cell behaviors should be coordinated consistently with the overall population dynamics and functions. However, the interrelation between single-cell rules and the population-level goal is still elusive. In this work, we reveal that these two levels are naturally connected via a gradient flow structure of heterogeneous cellular populations and that biologically prevalent single-cell rules, such as unidirectional type switching and hierarchical order in types, emerge from this structure. We also demonstrate the gradient flow structure in a standard model of the T-cell immune response. This theoretical framework works as a basis for understanding multicellular dynamics and functions.Received 26 May 2022Accepted 11 May 2023DOI:https://doi.org/10.1103/PhysRevResearch.5.L022052Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasBiological complexityCell processes & propertiesPopulation dynamicsPhysical SystemsCellsPopulationsNonlinear DynamicsStatistical PhysicsBiological Physics