Mulberry2020 - Three-layered, self-organizing multicellular structure where all cells randomly belong to one of the two genotypes
- 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 this revision: Nicola Mulberry
Modellers: Rahuman Sheriff, Nicola Mulberry
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|ThreeLayerCircuit_Fig7.xml||MorpheusML implementation built using Morpheus v2.1||9.06 KB||Preview | Download|
|Mulberry2020_Figs7_8_reproduced.mp4||Figure 7,8 Simulation movies generated using Morpheus v2.2-beta3||2.63 MB||Preview | Download|
- Model originally submitted by : Nicola Mulberry
- Submitted: Sep 25, 2020 1:00:02 PM
- Last Modified: Oct 12, 2021 5:32:03 PM
- Submitted on: Oct 12, 2021 5:32:03 PM
- Submitted by: Nicola Mulberry
- With comment: update model format
- Submitted on: Sep 25, 2020 1:00:02 PM
- Submitted by: Rahuman Sheriff
- With comment: Edited model metadata online.
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