BIO-LGCA: A cellular automaton modelling class for analysing collective cell migration

PLoS Comput Biol. 2021 Jun 15;17(6):e1009066. doi: 10.1371/journal.pcbi.1009066. eCollection 2021 Jun.

Abstract

Collective dynamics in multicellular systems such as biological organs and tissues plays a key role in biological development, regeneration, and pathological conditions. Collective tissue dynamics-understood as population behaviour arising from the interplay of the constituting discrete cells-can be studied with on- and off-lattice agent-based models. However, classical on-lattice agent-based models, also known as cellular automata, fail to replicate key aspects of collective migration, which is a central instance of collective behaviour in multicellular systems. To overcome drawbacks of classical on-lattice models, we introduce an on-lattice, agent-based modelling class for collective cell migration, which we call biological lattice-gas cellular automaton (BIO-LGCA). The BIO-LGCA is characterised by synchronous time updates, and the explicit consideration of individual cell velocities. While rules in classical cellular automata are typically chosen ad hoc, rules for cell-cell and cell-environment interactions in the BIO-LGCA can also be derived from experimental cell migration data or biophysical laws for individual cell migration. We introduce elementary BIO-LGCA models of fundamental cell interactions, which may be combined in a modular fashion to model complex multicellular phenomena. We exemplify the mathematical mean-field analysis of specific BIO-LGCA models, which allows to explain collective behaviour. The first example predicts the formation of clusters in adhesively interacting cells. The second example is based on a novel BIO-LGCA combining adhesive interactions and alignment. For this model, our analysis clarifies the nature of the recently discovered invasion plasticity of breast cancer cells in heterogeneous environments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biophysical Phenomena
  • Breast Neoplasms / pathology
  • Breast Neoplasms / physiopathology
  • Cell Adhesion / physiology
  • Cell Communication / physiology
  • Cell Movement / physiology*
  • Computational Biology
  • Computer Simulation
  • Female
  • Humans
  • Models, Biological*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / physiopathology
  • Systems Analysis*
  • Systems Biology

Grants and funding

HH acknowledges the funding support of the Helmholtz Association of German Research Centers—Initiative and Networking Fund for the project on Reduced Complexity Models (ZT-I-0010). HH is supported by MulticellML (01ZX1707C) of the Federal Ministry of Education and Research (BMBF) and the Volkswagenstiftung within the “Life?” programme (96732). AD acknowledges support by the EU-ERACOSYS project no. 031L0139B. JMNS acknowledges support from the PAPIIT-UNAM grant, project IA104821. SS is supported by the European Social Fund (ESF), co-financed by tax funds based on the budget adopted by the members of the Saxon State Parliament. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.