Use Cases

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Cell Sorting

You can do this experiment at home; place oil and water in a jar, shake vigorously and watch oil "cells" find other oil "cells". For biological cells this is a difficult experiment to perform because bio-cells are often responding to external conditions. Furthermore, to isolate sorting conditions one would have to knock-out genes responsible for other behaviors and this task is a few steps from easy.


Computationally Inspired Cell Sorting: http://biocomplexity.indiana.edu/jglazier/papers.php?action=view&id=3

Biologist, however, recognize the importance of cell sorting as an vital mechanism for development. DAH (differential adhesion hypothesis) is the term. For more info link

Images most likely will not need annotation at each step. Cell sorting can be completely described by a set of initial conditions (random mix of two cell types with different adhesion energies) and a description of final conditions (cell type green condensed in the center. cell type blue engulfed cell type green).

CompuCell can output all data in the simulation (COM location of all cells at each MCS, concentration of chemicals Image, volume of each cell, etc). In the case of cell sorting the image is really the only relevant data. You might also want COM of all cells at each MCS so you could measure heterotypic boundary length as a function of step, however, this measurement could be done with image analysis as well.


Ontology to Model

?->{sbml,cellml,function,ode,pde,float}

Experiment

  • Remove 12-day embryos from chick eggs.
  • Dissect out eyes.
  • Separate pigmented and retinal epithelial sheets.
  • Treat sheets separately with trypsin and dissociate into pigmented and retinal cell suspensions.
  • Mix at desired concentration.
  • Pellet
  • Cut pellet to desired size, approximately 5x103 cells .
  • Suspend pellet in hanging-drop culture and observe under 20x or 40x objective.
  • Experimental Observation: The black cells form clusters and eventually sort into s spheroid surrounded by the translucent cells. The sorting takes about 72 hours.

Biological Modeling

  • Two cell types: Pigmented Retinal and Neural Retinal.
  • Pigmented Retinal Cells are black, have a volume of approximately ?? μm3 and express high levels of N-CAMs. They are motile and essentially mesenchymal in characteristics (despite their name). They do not divide or differentiate during the experiment and their other properties remain essentially constant.
  • Neural Retinal Cells are translucent, have a volume of approximately {\frac{??}{4}}{\mu} m^3 and express low levels of N-CAMs. They are motile to approximately the same degree as Pigmented Retinal Cells and essentially mesenchymal in characteristics (despite their name). They do not divide or differentiate during the experiment and their other properties remain essentially constant.
  • Initial condition: A spheroid of closely packed, randomly mixed, Pigmented and Neural Retinal Cells in contact with a fluid medium of Eagles DMEM+ Horse Serum.

CompuCell3D Modeling 

<CompuCell3D>
 <Potts>
  <Dimensions x="100" y="100" z="1"/>
  <Anneal>10</Anneal>
  <Steps>10000</Steps>
  <Temperature>10</Temperature>
  <Flip2DimRatio>1</Flip2DimRatio>
  <NeighborOrder>2</NeighborOrder>
 </Potts>
 <Plugin Name="Volume">
  <TargetVolume>25</TargetVolume>
  <LambdaVolume>2.0</LambdaVolume>
 </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">16</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>
   <NeighborOrder>2</NeighborOrder>
  </Plugin>
  <Steppable Type="BlobInitializer">
    <Region>
      <Radius>30</Radius>
      <Center x="40" y="40" z="0"/>
      <Gap>0</Gap>
      <Width>5</Width>
     <Types>Condensing,NonCondensing</Types>
    </Region>
  </Steppable> 
</CompuCell3D>

Ontological Model 

o  Cell Type: PigmentedRetinalEpithelialCell:
 + IsA Cell IsA CellLevel IsA Biological IsA Entity
       # Is Mesenchymal IsA PropertyRelatedToEntities
 + IsA MesenchymalCell IsA CellType
 + ParticipatesIn Volume IsA PropertiesRelatedToEntities
 + HasRestriction Volume IsA  SpatialRestriction IsA Restriction
       # HasRestriction Large IsA Quality IsA Restriction
 + ParticipatesIn Shape IsA PropertiesRelatedToEntities
 + HasRestriction Isotropic IsA  SpatialRestriction IsA Restriction
 + ParticipatesIn Location IsA PropertiesRelatedToEntities
 + ParticipatesIn Color IsA PropertiesRelatedToEntities
 + HasRestriction Color IsA PropertiesRelatedToEntities
       # HasRestriction Black IsA Quality IsA Restriction
 + Has Capacity IsA Actualization
       # Movement IsA Behavior IsA Process
             * HasRestriction Random IsA PropertyRelatedToBehaviors
       # CellCellAdhesion IsA Behavior IsA Process
             * HasParticipants Cells IsA CellLevel IsA Biological IsA Entity
                   o Using N-CAM IsA AdhesionMolecule IsA Method (???)
                         + HasProperty Transient IsA PropertyRelatedToCellBehaviors
                         + HasQuality Much IsA Amount IsA Restriction
             * HasParticipants Fluid IsA Nonbiological IsA Entity
                   o HasRestriction Weakly IsA PropertyRelatedToBehaviors
 + Has Actual IsA Actualization
       # Movement IsA Behavior IsA Process
             * HasRestriction Random IsA PropertyRelatedToBehaviors

o Cell Type: NeuralRetinalEpithelialCell:
 + IsA Cell IsA CellLevel IsA Biological IsA Entity
       # Is Mesenchymal IsA PropertyRelatedToEntities
 + IsA MesenchymalCell IsA CellType
 + ParticipatesIn Volume IsA PropertiesRelatedToEntities
 + HasRestriction Volume IsA  SpatialRestriction IsA Restriction
       # HasRestriction Small IsA Quality IsA Restriction
 + ParticipatesIn Shape IsA PropertiesRelatedToEntities
 + HasRestriction Isotropic IsA  SpatialRestriction IsA Restriction
 + ParticipatesIn Location IsA PropertiesRelatedToEntities
 + ParticipatesIn Color IsA PropertiesRelatedToEntities
 + HasRestriction Color IsA PropertiesRelatedToEntities
       # HasRestriction Translucent IsA Quality IsA Restriction
 + Has Capacity IsA Actualization
       # Movement IsA Behavior IsA Process
             * HasRestriction Random IsA PropertyRelatedToBehaviors
       # Adhesion IsA Behavior IsA Process
             * HasParticipants Cells IsA CellLevel IsA Biological IsA Entity
                   o Using N-CAM IsA AdhesionMolecule IsA Method (???)
                         + HasProperty Transient IsA PropertyRelatedToCellBehaviors
                         + HasQuality Little IsA Amount IsA Restriction
             * HasParticipants Fluid IsA Nonbiological IsA Entity
                   o HasRestriction Weakly IsA PropertyRelatedToBehaviors
 + Has Actual IsA Actualization
       # Movement IsA Behavior IsA Process
             * HasRestriction Random IsA PropertyRelatedToBehaviors

o Medium: DMEM:
 + IsA Fluid IsA NonBiological IsA Entity
o InitialCondition:
 + CellAggregate IsA SuperCellular IsA Entity 
 + ParticipatesIn Volume IsA PropertiesRelatedToEntities
 + HasRestriction Volume IsA  SpatialRestriction IsA Restriction
 + ParticipatesIn Shape IsA PropertiesRelatedToEntities
 + HasRestriction Sphere IsA  SpatialRestriction IsA Restriction
 + ParticipatesIn Location IsA PropertiesRelatedToEntities
 + Has Restriction Location IsA SpatialRestriction IsA Restriction
 + HasParticipants PigmentedRetinalEpithelialCells IsA CellType
 + HasParticipants NeuralRetinalEpithelialCells IsA CellType

ML Version of Ontology 

<Cell Type Name=“PigmentedRetinalEpithelialCell”>
 <Volume>???<\Volume>
 <Color> Dark<\Color>
 <Motility Type=“Random”>???<\Motility>
 <Adhesion Type=“N-CAM”>???<\Adhesion>
 <Adhesion Type=“Fluid”>???<\Adhesion>
<\Cell Type>
<Cell Type Name=“NeuralRetinalEpithelialCell”>
 <Volume>???<\Volume>
 <Color> Light<\Color>
 <Motility Type=“Random”>???<\Motility>
 <Adhesion Type=“N-CAM”>???<\Adhesion>
 <Adhesion Type=“Fluid”>???<\Adhesion>
<\Cell Type>
<ECMType Name=“Medium”>
 <Type>Fluid<\Type>
<\ECMType>
<InitialConditions>
 <Shape>Sphere<\Shape>
 <Radius>???<\Radius>
 <Components Type=“PigmentedRetinalEpithelialCell” Percentage=??? Type=“NeuralRetinalEpithelialCell” Percentage=????>
 <SpatialDistribution>Random<\SpatialDistribution>
 <\InitialConditions>
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