2D Cell Communication Model

[Madhav Binuraj Nair]

Hi
I was wondering if it would be possible to create a model where each cell has a genetic circuit defining its phenotype and the cells can either inhibit or activate cells in its neighbourhood based on its phenotype, wthin a certain radius. At the same time the cells undergo cell division and are able to move around.

Regards

Madhav

[Lutz Brusch]

Hi Madhav,

sure, what you describe is a fundamental developmental process and a focus of many Morpheus models (and fun to simulate with Morpheus). There are several simple models that you may open from the GUI and change/extend to your needs, incl.

- Examples/Multiscale/AutocrineChemotaxis (cells move around and secrete a diffusible signal with a tunable interaction range as function of diffusion and decay rates): https://identifiers.org/morpheus/M0031

- Examples/ODE/MAPK-Signaling (derived from an SBML model, major signaling pathway that feeds into gene regulation): https://identifiers.org/morpheus/M0002

- Examples/Miscellaneous/FrenchFlag (has a threshold-dependent genetic mini-circuit): https://identifiers.org/morpheus/M0042

and from the model repository, you can load

- Published/Principles/Morphodynamics3 (with a gene circuit that also changes Delta ligand expression on the cell, this ligand is then sensed by Notch receptors on adjacent cells and feeds into their gene circuit): https://identifiers.org/morpheus/M2053

- Contributed Examples/Multiscale/DiffusibleSignal (conserves the mass of a diffusible signal across secretion-diffusion-uptake): https://identifiers.org/morpheus/M5491

Regarding your activation/inhibition signal "within a certain radius", you have to choose from or combine some of the following mechanisms depending on the size of your "radius":

- The biological mechanisms of your experimental system may involve cell-cell contact signals, then see the Delta-Notch-based model Morphodynamics3 (and its sister models ...1, ...2) above. Here, the signaling "radius" is just one cell diameter. 

- Or they may involve secreted molecules (see AutocrineChemotaxis and DiffusibleSignal above) and then the signaling "radius" is approximately given by sqrt(D/k) with diffusion constant D and decay rate k.

- Or your cells use longer cytonemes of a length that corresponds to several cell diameters. Then you may use a signal radius counter in surrounding cells as it was used in a liver regeneration model (see top-left panel in that model's plots/movie): https://identifiers.org/morpheus/M9147

If you run into a particular issue as you set up your model, then we'll find a solution here.

Best,

Lutz (for Morpheus.lab)

[Madhav Binuraj Nair]

I see thanks a lot, I will try them out

[Madhav Binuraj Nair]

I was playing around with the lateral signalling example and I was wondering if there was a way to introduce cell division into that system similar to the 2D cell proliferation example?

[Madhav Binuraj Nair]

Hi Lutz

I was wondering if you could help me figure out how we could add cell division to the lateral signalling example, because when I try to add CellDivision property to the simulation the simulation does not seem to proceed forward.

[Lutz Brusch]

Hi Madhav,
the lateral signaling example had used a minimal cell representation of just one (hexagonal shaped) lattice element per cell. CellDivision cannot divide such a single lattice element.
In the attached model, I've given each cell between 50 and 100 lattice elements and now CellDivision (controllable by new parameters in Global) increases the cell number from 36 to 300 while lateral signaling is simultaneously simulated (note the two CellType/Systems, one for the cell cycle and one for signaling) and influenced by the changing cell neighbors.

The cell cycle is set to stop at half runtime to see how the signaling pattern relaxes (above snapshots are at t=10, 30).
Upon cell division, both daughter cells inherit the signaling state of the mother cell. You may use CellDivision/Trigger to change that (as is used already to give each daughter cell an individual volume growth rate).
Best,
Lutz