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CompuCell3D: A Morphogenesis

simulation package

Nan Chen and Mark Alber

2/20/2006

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Topics

● Introduction to CompuCell3D

● Cellular Potts Model

● Framework of CompuCell3D

● Usage of CompuCell3D

● Future Plans

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Introduction to CompuCell3D

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● Morphogenesis simulation package based on Cellular Potts Model (CPM)

● Capable of modeling cell clustering as well as growth, division, death, intracellular adhesion, and volume and surface area constraints

● Partial differential equation models for external chemical fields which can model reaction-diffusion

● Cell type automata provides a method for categorizing cells by behavior into types and algorithms for changing cell type

● Chemotaxis and haptotaxis

CompuCell3D overview

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CompuCell3D overview

● Framework design allow scientists to focus on

simulation development

– Visualization tool (CompCell Player)

– Standard input (XML) make the package easy to use

– Minimize the amount of coding required

● Flexible simulation framework

– Software design Pattern and Plug in feature

– Easy to extend and add new features

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● Cell sorting

● Limb bud growth

● Amoeba migration

● Dictyostelium discoideum

● Somites formation

CompuCell3D Applications

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Simple set-up of the Cellular Potts Model (CPM) (a) Initial condition, (b-d) results for

various bond-strength settings between dark cells, light cells and the surrounding

medium.

Cell Sorting

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Left. Skeletal Pattern formation: Time-series of

chick limb-bud development. Right. 3D cell

condensation and patterning into skeletal

elements- humerus, ulna+radius, and digits in a

chicken limb.

Limb bud growth

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Cellular Potts Model

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Cell structure is discretized into a cell map, each number in the above cell map corresponds to one cell.

Cellular Potts Model

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•System Hamiltonian consists of adhesion energy, volume energy and chemical energy•Transition probability, W, is determined by the change of free energy due to orientation alteration. G, according to above equation.

Cellular Potts Model

01

0)exp(

G

Gkt

Gw

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Cellular Potts Model• Energy minimization formalism

– extended by Graner and Glazier, 1992

• DAH: Contact energy depending on cell types (differentiated cells)

• Extensions:

– J_cell_cell is type dependent

– Other terms: Cell volume, Chemotaxis/Haptotaxis

• Metropolis algorithm: probability of configuration change

01

0)exp(

G

Gkt

Gw

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Framework of CompuCell3D

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CompuCellPlayer

User

XML input

CompuCell3D Kernal

Information flow chart for CompuCell3D

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Visualization tool●Using QT Lib●3D Visualization●2D Cross-section●Zooming, rotating, translating ●Picture Generation●pause a simulation

CompuCellPlayer

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CompuCell3D - XML input <Potts> <Dimensions x=“51" y=“51" z="21"/> <Steps>10</Steps> <Temperature>2</Temperature> <Flip2DimRatio>1</Flip2DimRatio> </Potts>

VolumevolumevolumeEnergy(cell)

<Plugin Name="Volume"> <TargetVolume>64</TargetVolume> <LambdaVolume>0.05</LambdaVolume> </Plugin>

SurfaceareasurfaceEnergy(cell)

<Plugin Name="Surface"> <TargetSurface>77</TargetSurface> <LambdaSurface>0.05</LambdaSurface> </Plugin>

ContactcontactEnergy( cell1, cell2)

<Plugin Name="Contact"> <Energy Type1="Medium" Type2="Medium">0</Energy> <Energy Type1="Light" Type2="Medium">0</Energy> <Energy Type1="Dark" Type2="Medium">0.1</Energy> <Energy Type1="Light" Type2="Light">0.5</Energy> <Energy Type1="Dark" Type2="Dark">3.0</Energy> <Energy Type1="Light" Type2="Dark">0.5</Energy> </Plugin>

Potts ModelDefination

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CompuCell3D Structure

Steppables are executed once per Monte Carlo step and once before and after the main loop. They are the main hooks for initialization and rendering.

Steppers are executed once per spin flip attempt. They are the main hooks for energy functions.

CellChangeWatchers are executed once per each successful spin flip. They are useful for adjusting values that depend on the number of lattice points in a cell.

Automatons enable cell state to change their state as the simulation evolves.

Plugins are loaded at runtime. They are the main way of adding new features to CompuCell. They can be Steppables, Steppers, CellChangeWatchers, or Automatons.

Initialization()

Steppables.Start()

For each Monte Carlo step:

For flip attempt: if(flip): CellChangeWatcher(cell) Automatons.Update(cell) Steppers.step()

Steppabless.step() Steppables.finish()

CompuCell3D Program Flow

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Quickstart Guide of CompuCell3D

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Installation

● For testing purpose, you could directly install binary package

– Easy to install

● For development purpose, you could download source code and compile it

– Your computer needs to have automake, autoconfigure, autohead, libtool package

● You could find this package from simtk.org

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Mcs 0 Mcs 50

Mcs 100

Your first example-Foam simulation

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<CompuCell3D> <Potts> <Dimensions x="101" y="101" z="1"/> <Anneal>0</Anneal> <Steps>100</Steps> <Temperature>5</Temperature> <Flip2DimRatio>1</Flip2DimRatio> <Boundary_y>Periodic</Boundary_y> <Boundary_x>Periodic</Boundary_x> <FlipNeighborMaxDistance>1.75</FlipNeighborMaxDistance> </Potts> <Plugin Name="CellType"> <CellType TypeName="Medium" TypeId="0"/> <CellType TypeName="Foam" TypeId="1"/> </Plugin> <Plugin Name="Contact"> <Energy Type1="Foam" Type2="Foam">20</Energy> <Energy Type1="Medium" Type2="Medium">100</Energy> <Energy Type1="Medium" Type2="Foam">100</Energy> <Depth>1.5</Depth> </Plugin> <Steppable Type="PIFInitializer"> <PIFName>Foam_1.pif</PIFName> </Steppable> </CompuCell3D>

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Your first example

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Setting for Potts Model

<Potts>

<Dimensions x="101" y="101" z="1"/>

<Anneal>0</Anneal>

<Steps>100</Steps>

<Temperature>5</Temperature>

<Flip2DimRatio>1</Flip2DimRatio>

<Boundary_y>Periodic</Boundary_y>

<Boundary_x>Periodic</Boundary_x>

<FlipNeighborMaxDistance>1.75</FlipNeighborMaxDistance>

</Potts>

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<Plugin Name="CellType">

<CellType TypeName="Medium" TypeId="0"/>

<CellType TypeName="Foam" TypeId="1"/>

</Plugin>

<Plugin Name="Contact">

<Energy Type1="Foam" Type2="Foam">20</Energy>

<Energy Type1="Medium" Type2="Medium">100</Energy>

<Energy Type1="Medium" Type2="Foam">100</Energy>

<Depth>1.5</Depth>

</Plugin>

Setting for Cell type and Contact energy

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1 Foam 1 5 1 5 0 02 Foam 1 5 6 10 0 03 Foam 1 5 11 15 0 04 Foam 1 5 16 20 0 05 Foam 1 5 21 25 0 06 Foam 1 5 26 30 0 07 Foam 1 5 31 35 0 08 Foam 1 5 36 40 0 09 Foam 1 5 41 45 0 0

<Steppable Type="PIFInitializer">

<PIFName>Foam_1.pif</PIFName>

</Steppable>

PIF File

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./FoamInit.pl -r5 -i60 -ofoaminit1.pif -z2 -m10Lattice dimension: x_max=301 y_max=301 z_max=1

<Dimensions x="301" y="301" z="1"/>

PIF Generator

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<Potts> <Dimensions x="101" y="101" z="1"/> <Anneal>0</Anneal> <Steps>1000</Steps> <Temperature>500</Temperature><Temperature>500</Temperature> <Flip2DimRatio>1</Flip2DimRatio> <Boundary_y>Periodic</Boundary_y>

5 500

Change temperature

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<Plugin Name="Contact"> <Energy Type1="Foam" Type2="Foam">200</Energy> <Energy Type1="Medium" Type2="Medium">1</Energy> <Energy Type1="Medium" Type2="Foam">1</Energy> <Depth>1.5</Depth> </Plugin>

Mcs 50 Mcs 100Mcs 0

Change Contact energy

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5 4 3 4 5

4 2 1 2 4

3 1 x 1 3

4 2 1 2 4

5 4 3 4 5

<Potts>

<Dimensions x="101" y="101" z="1"/>

<Anneal>0</Anneal>

<Steps>100</Steps>

<Temperature>5</Temperature>

<Flip2DimRatio>1</Flip2DimRatio>

<Boundary_y>Periodic</Boundary_y>

<Boundary_x>Periodic</Boundary_x>

<FlipNeighborMaxDistance>1.75</FlipNeighborMaxDistance>

</Potts>

<Plugin Name="Contact">

<Energy Type1="Foam" Type2="Foam">20</Energy>

<Energy Type1="Medium" Type2="Medium">100</Energy>

<Energy Type1="Medium" Type2="Foam">100</Energy>

<Depth>1.5</Depth>

</Plugin>

Order of Neighbor

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<Plugin Name="Contact"> <Energy Type1="Foam" Type2="Foam">20</Energy> <Energy Type1="Medium" Type2="Medium">200</Energy> <Energy Type1="Medium" Type2="Foam">200</Energy> <Depth>1.1</Depth> </Plugin>

1.1 1.5 2.7

Order of Neighbor

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<Potts> <Dimensions x="101" y="101" z="1"/> <Anneal>0</Anneal> <Steps>100</Steps> <Temperature>5</Temperature> <Flip2DimRatio>1</Flip2DimRatio> <Boundary_y>Periodic</Boundary_y> <Boundary_x>Periodic</Boundary_x> <FlipNeighborMaxDistance>1.1</FlipNeighborMaxDistance> </Potts>

<Depth>1.1</Depth>

Temperature 20 Temperature 5

Temperature effect on Low Order of Neighbor

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Initial

Cell Sorting

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<CompuCell3D> <Potts> <Dimensions x="70" y="70" z="1"/> <Anneal>10</Anneal> <Steps>10000</Steps> <Temperature>5</Temperature> <Flip2DimRatio>1</Flip2DimRatio> <FlipNeighborMaxDistance>1.75</FlipNeighborMaxDistance> </Potts><Plugin Name="Volume"> <TargetVolume>9</TargetVolume> <LambdaVolume>3.0</LambdaVolume> </Plugin> <Plugin Name="Surface"> <TargetSurface>16</TargetSurface> <LambdaSurface>0.5</LambdaSurface> </Plugin><Plugin Name="CellType"> <CellType TypeName="Medium" TypeId="0"/> <CellType TypeName="Condensing" TypeId="1"/> <CellType TypeName="NonCondensing" TypeId="2"/> </Plugin> <Plugin Name="Contact"> <Energy Type1="Medium" Type2="Medium">0</Energy> <Energy Type1="NonCondensing" Type2="NonCondensing">14</Energy> <Energy Type1="Condensing" Type2="Condensing">2</Energy> <Energy Type1="NonCondensing" Type2="Condensing">11</Energy> <Energy Type1="NonCondensing" Type2="Medium">16</Energy> <Energy Type1="Condensing" Type2="Medium">16</Energy> <Depth>1.75</Depth> </Plugin> <Plugin Name="CenterOfMass"/> <Steppable Type="OutputData"/> <Steppable Type="BlobInitializer"> <Gap>0</Gap> <Width>2</Width> <CellSortInit>yes</CellSortInit> <Radius>20-</Radius> </Steppable></CompuCell3D>

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XML file for Cell Sorting

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<Plugin Name="Volume">

<TargetVolume>9</TargetVolume>

<LambdaVolume>3.0</LambdaVolume>

</Plugin>

<Plugin Name="Surface">

<TargetSurface>16</TargetSurface>

<LambdaSurface>0.5</LambdaSurface>

</Plugin>

<Plugin Name="CellType">

<CellType TypeName="Medium" TypeId="0"/>

<CellType TypeName="Condensing" TypeId="1"/>

<CellType TypeName="NonCondensing" TypeId="2"/>

</Plugin>

<Plugin Name="Contact">

<Energy Type1="Medium" Type2="Medium">0</Energy>

<Energy Type1="NonCondensing" Type2="NonCondensing">14</Energy>

<Energy Type1="Condensing" Type2="Condensing">2</Energy>

<Energy Type1="NonCondensing" Type2="Condensing">11</Energy>

<Energy Type1="NonCondensing" Type2="Medium">16</Energy>

<Energy Type1="Condensing" Type2="Medium">16</Energy>

<Depth>1.75</Depth>

</Plugin>

Energy setting

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<Steppable Type="BlobInitializer">

<Gap>0</Gap>

<Width>2</Width>

<CellSortInit>yes</CellSortInit>

<Radius>20-</Radius>

</Steppable>

Initial structure setting

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Future Plans

● We want to hear from you● Shell language interface

– As matlab, FemLab● Parallelizing