Is cell segregation like oil and water: Asymptotic versus transitory regime

PLoS Comput Biol. 2022 Sep 19;18(9):e1010460. doi: 10.1371/journal.pcbi.1010460. eCollection 2022 Sep.

Abstract

Understanding the segregation of cells is crucial to answer questions about tissue formation in embryos or tumor progression. Steinberg proposed that separation of cells can be compared to the separation of two liquids. Such a separation is well described by the Cahn-Hilliard (CH) equations and the segregation indices exhibit an algebraic decay with exponent 1/3 with respect to time. Similar exponents are also observed in cell-based models. However, the scaling behavior in these numerical models is usually only examined in the asymptotic regime and these models have not been directly applied to actual cell segregation data. In contrast, experimental data also reveals other scaling exponents and even slow logarithmic scaling laws. These discrepancies are commonly attributed to the effects of collective motion or velocity-dependent interactions. By calibrating a 2D cellular automaton (CA) model which efficiently implements a dynamic variant of the differential adhesion hypothesis to 2D experimental data from Méhes et al., we reproduce the biological cell segregation experiments with just adhesive forces. The segregation in the cellular automaton model follows a logarithmic scaling initially, which is in contrast to the proposed algebraic scaling with exponent 1/3. However, within the less than two orders of magnitudes in time which are observable in the experiments, a logarithmic scaling may appear as a pseudo-algebraic scaling. In particular, we demonstrate that the cellular automaton model can exhibit a range of exponents ≤1/3 for such a pseudo-algebraic scaling. Moreover, the time span of the experiment falls into the transitory regime of the cellular automaton rather than the asymptotic one. We additionally develop a method for the calibration of the 2D Cahn-Hilliard model and find a match with experimental data within the transitory regime of the Cahn-Hilliard model with exponent 1/4. On the one hand this demonstrates that the transitory behavior is relevant for the experiment rather than the asymptotic one. On the other hand this corroborates the ambiguity of the scaling behavior, when segregation processes can be only observed on short time spans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Separation
  • Motion*

Grants and funding

The authors A.V.-B., S.L., H.-J.B., F.F. acknowledge that this research is co-financed by the EU, the European Social Fund (ESF) and by tax funds on the basis of the budget passed by the Saxon state parliament: SAB-Nr. 100382145. Further, A.V.-B and F.F. acknowledge support by Sächsisches Staatsministerium für Wissenschaft und Kunst (SMWK) project FORZUG II TP 3. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.