Modelling multicellular system

[Deepa]

Hi All,

I am trying to build a simple model to understand cell to cell communication. 

To start with, I want to model the diffusion of a drug molecule from one cell to an adjacent cell. If there are examples of such a system that is already set up and simulated in COPASI, could someone please share a reference link?

Thanks,

Deepa

[Mendes,Pedro]

Hello Deepa,

If you want to model the transport of a drug from one cell to another that is possible in COPASI. However if you really want to model diffusion (as in a spatial gradient of concentration) then COPASI cannot do that.

For transport between cells, something like this would work:

The transport is modeled by this reaction (I am assuming that it is reversible, but you can also make it reversible):

Drug_cell1 = Drug _cell2

Then you have to set up two compartments:

Cell1 - add its volume
Cell2 - add its volume

then set Drug_cell1 to be in the compartment "Cell1" and set Drug_cell2 to be in compartment "Cell2"

finally you want to select an appropriate kinetic type for the reaction. Note that transport between cells is likely dependent on the number of transporters that exist between cells (gap junctions, etc), in that case a regular Michaelis Menten type would suffice (the Vmax is proportional to the number of channels between cells). If you want the molecule to be able to diffuse between cells, across membranes, then you will need to know the surface area of contact between cells and incorporate that in a new kinetic type.

(Note that there is quite some evidence that drugs don't go across membranes freely, see this recent review on the topic:
https://doi.org/10.3390/molecules26185629)

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-- 
Pedro Mendes, PhD
Professor and Director,
Richard D. Berlin Center for Cell Analysis and Modeling
University of Connecticut School of Medicine
group website: http://www.comp-sys-bio.org

[Blinov,Michael]

Hi Deepa,

You can try Virtual Cell software (https://vcell.org) where you can define arbitrary cell geometry and model diffusion. There are multiple tutorials (e.g. the first one at https://vcell.org/support) where you can see how compartments and diffusion are modeled. Questions to vcell-...@googlegroups.com​ 

Best,

Michael

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[Deepa]

Dear Prof. Mendes,

Thanks a lot for the review article link that you have provided. This is really helpful.

I would like to request for a few more clarifications if you don't mind.

Would it be appropriate to model metabolite(say, glucose) transport between two cells via diffusion?

I am interested in modelling the coupling between the two cells using an expression like the below without accounting for

the efflux of biochemicals from the cell to the extracellular fluid and influx of the chemical into neighbouring cells from the fluid.

dS_i/dt =  -P(Si - Sj) where the units of P is in per second (1/s), i and j are the indices of cell 1 and cell 2.

I am slightly confused about the units in which P should be defined because if I use the normal units of diffusion coefficients (m^2/s)

then there will be issues when the volume of cells 1 and 2 are different. To define the right units, I should multiply D (if set in m^2/s) by a

length factor and I am not sure how this length has to be defined ( should it be center to center distance of cells?, I am confused.)

If there are models that study metabolite exchange between cells, could you please share some reference links?

Thanks a lot for your time and kind attention,

Deepa

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[Deepa]

Hi  Michael,

Thanks a lot, I had a chance to go through the examples. I will post my further questions on VCell forum.

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