Mulberry2020 - Two-layered, self-organizing multicellular structure where all cells are one of the two genotypes

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This model generates a two-layered, multicellular structure from a simple cell-cell signaling model. The cell signaling model is described by a system of ordinary differential equations, and is coupled with a cellular potts model. The model is in the MorpheusML format ( The model will initialize with a random configuration of cells (which can be one of two types) which will then self-organize to form a two-layered structure. This file was used to produce Figure 2 in Mulberry and Keshet, 2020.
Related Publication
  • Self-organized multicellular structures from simple cell signaling: a computational model
  • Nicola Mulberry, Leah Edelstein-Keshet
  • Physical Biology , 8/ 2020 , DOI: 10.1088/1478-3975/abb2dc
  • Simon Fraser University, University of British Columbia
  • Recent synthetic biology experiments reveal that signaling modules designed to target cell-cell adhesion enable self-organization of multicellular structures [Toda, 2018]. Changes in homotypic adhesion that arise through contact-dependent signaling networks result in sorting of an aggregate into two- or three-layered structures. Here we investigate the formation, maintenance, and robustness of such self-organization in the context of a computational model. To do so, we use an established model for Notch/Ligand signaling within cells to set up differential E-cadherin expression. This signaling model is integrated with the Cellular Potts Model to track state changes, adhesion, and cell sorting in a group of cells. The resulting multicellular structures are in accordance with those observed in the experimental reference. In addition to reproducing these experimental results, we track the dynamics of the evolving structures and cell states to understand how such morphologies are dynamically maintained. This appears to be an important developmental principle that was not emphasized in previous models. Our computational model facilitates more detailed understanding of the link between intra- and intercellular signaling, spatio-temporal rearrangement, and emergent behaviour at the scale of hundred(s) of cells.
Submitter of the first revision: Nicola Mulberry
Submitter of this revision: Nicola Mulberry
Modellers: Rahuman Sheriff, Nicola Mulberry

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Model files

SingleGenotype_Fig10.xml MorpheusML implementation built using Morpheus v2.1 5.15 KB Preview | Download

Additional files

Mulberry2020_Fig10_reproduced.mp4 Simulation movies generated using Morpheus v2.2-beta3 2.78 MB Preview | Download

  • Model originally submitted by : Nicola Mulberry
  • Submitted: Sep 25, 2020 12:53:02 PM
  • Last Modified: Oct 12, 2021 5:30:52 PM
  • Version: 6 public model Download this version
    • Submitted on: Oct 12, 2021 5:30:52 PM
    • Submitted by: Nicola Mulberry
    • With comment: Update title and model format.
  • Version: 4 public model Download this version
    • Submitted on: Sep 25, 2020 12:53:02 PM
    • Submitted by: Rahuman Sheriff
    • With comment: Edited model metadata online.

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