A step-by-step guide to exploring and simulating the yeast MAPK model


1. Creating the Yeast Cell Morphology with Shmoo

  1. Start the Simmune CellDesigner.

  2. Set the dimensions of the compartment to Width=45, Height and Length=25.

  3. Click "New Cell" and "Center Cells".

  4. Deselect "Show Ruler". Increase the size of the Cell to 1189 cubic microns (at a grid constant of 1 micron). Note: Cells in the CellDesigner are composed of "Protrusions". A cell contains at least one, the fundamental protrusion determining the spatial origin of the cell. This protrusion can only be modified in size. Modifying its position means moving the cell. Additional protrusions can be moved relative to the fundamental protrusion to permit creating (almost) any (simply-connected) cell shape. The protrusion should have a size of 12.

  5. Click "New Protrusion". Note that the new protrusion is hidden in the fundamental protrusion. Move its x Position to make it visible. When it leaves the fundamental protrusion the cell size increases. Note that you can regulate size and positions of protrusions independently for each protrusion.

  6. Move the second protrusion to an x-position of 5 (it will then be hidden again in the larger first protrusion). Increase its size to 7. Note that you can see the contrinution of a protrusion within a cell by moving the mouse over its controls.

  7. Create a third protrusion at position x=10 and size 6.

  8. Create a fourth protrusion at position x=14 and size 5.

  9. Create a fifth protrusion at position x=19 and size 5.

  10. In order to reproduce exactly the cell shape that was used in the manuscript we now use a protrusion with negative size. Such protrusions are subtracted from the cell geometry. Create a protrusion at x=22. This protrusion (if it has size 2) is hidden in the last protrusion we created (at x=19).

  11. Now set the size of the protrusion at x=22 to -3. This will remove the end of the tip, thereby adjusting the cell shape to what was used in the yeast MAPK simulations. 'Negative' protrusions in general can be used to remove unwanted regions from cell shapes. You can also use them to create indentations in cell surfaces. Note that the simulations would work just as well with the tip protrusion as it was before adding the negative protrusion.

  12. Now, we will create a nucleus. Set "Nucleus" as "Edit Mode".

  13. The cell surface now is transparent so we will be able to see the nucleus.

  14. Click "New Source".

  15. 15) Resize the source of the nucleus to size 5.5 and move it to x=6. Note that you can use the mouse wheel to zoom into the display.

  16. Add a second and a third source. Position them at x=9 and x=3 and resize them to 1.5. (Note: even though the display shows a source as a one-cube element for sizes 0.5, 1, 1.5 the internal representation has a higher resolution. If you change the size of one of the two smaller sources to 1 you will see a difference.)

  17. Now, we create the Regions for populating the biochemistry of the cell differently in the Shmoo tip and the residual cell body. Set "Regions" as "Edit Mode".

  18. Then click "New Region". Resize and move the Region until it just covers the cell except for a small region at the tip.

  19. Click "New Region" and resize and move the new Region until it covers the tip. Note that the two regions repell each other.

  20. Call the first Region "Body", the second region "Shmoo".

  21. Go back to the "Geometry" "Edit Mode". Select "Show Ruler" and draw a line (click, draw, click) to position the ruler anywhere.

  22. Move the ruler until its ends coincide with the tip ...

  23. and the end (along the x-axis) of the cell.

  24. Enter "7.5" in the text field next to the "Rescale Ruler length to" button. Then click the button. Note how the Grid Constant and the Volume of the cell has changed. The cell is now 7.5 microns long.

  25. Click "Save" and then enter a name for the geometry file (e.g. "Yeast.geo"). Click "Save" in the dialog. Close the CellDesigner.