lysis location logging, proliferative antigen tracking, matrigel non-migration option

Author: allison-li-1016

src/arcade/patch/agent/cell/PatchCellCART.java

@@ -380,8 +380,14 @@ private double calculateMichaelisMenten(
             int startReceptors,
             double alpha,
             double beta) {
+
+        double correctedStartReceptors = startReceptors;
+
+        if (startReceptors == 0) {
+            correctedStartReceptors = 1;
+        }
         return (targets * contactFraction / (affinity * beta + targets * contactFraction))
-                * (currentReceptors / startReceptors)
+                * (currentReceptors / correctedStartReceptors)
                 * alpha;
     }
 

src/arcade/patch/agent/cell/PatchCellCARTCombined.java

@@ -60,6 +60,10 @@ public PatchCellContainer make(int newID, CellState newState, MersenneTwisterFas
     public void step(SimState simstate) {
         Simulation sim = (Simulation) simstate;
 
+        if (sim.getSchedule().getTime() == 2880) {
+            int a = 0;
+        }
+
         super.age++;
 
         if (state != State.APOPTOTIC && age > apoptosisAge) {

src/arcade/patch/agent/cell/PatchCellCARTCombinedCombinatorial.java

@@ -120,7 +120,17 @@ protected void checkForBinding(SimState simstate) {
      * @param sim the simulation instance
      */
     protected void calculateCARS(MersenneTwisterFast random, Simulation sim) {
+        // T cell cannot bind if no synnotch receptors are available
+        if (synnotchs == 0) {
+            if (boundSynNotch != 0) {
+                boundSynNotch = 0;
+            }
+            return;
+        }
+
+        // unbound synnotch should never be negative
         int unboundSynNotch = synnotchs - boundSynNotch;
+        unboundSynNotch = Math.max(0, unboundSynNotch);
 
         double expectedBindingEvents =
                 bindingConstant
@@ -130,14 +140,26 @@ protected void calculateCARS(MersenneTwisterFast random, Simulation sim) {
                         * contactFraction
                         * TAU;
 
+        // binding events should not exceed available unbound receptors
+        expectedBindingEvents = Math.min(expectedBindingEvents, unboundSynNotch);
+
         int bindingEvents = poissonFactory.createPoisson(expectedBindingEvents, random).nextInt();
         double expectedUnbindingEvents = unbindingConstant * boundSynNotch * TAU;
+
+        expectedUnbindingEvents = Math.min(expectedUnbindingEvents, boundSynNotch);
+
+        // unbinding events should not exceed available bound receptors
         int unbindingEvents =
                 poissonFactory.createPoisson(expectedUnbindingEvents, random).nextInt();
 
         boundSynNotch += bindingEvents;
         boundSynNotch -= unbindingEvents;
+
+        // bound synnotch should never be negative
+        boundSynNotch = Math.max(0, boundSynNotch);
         boundCell.updateSynNotchAntigens(unbindingEvents, bindingEvents);
+
+        // synnotch receptors become unavailable after binding
         synnotchs = Math.max(0, synnotchs - bindingEvents);
     }
 

src/arcade/patch/agent/cell/PatchCellCARTCombinedInducible.java

@@ -96,7 +96,7 @@ protected void calculateCARS(MersenneTwisterFast random, Simulation sim) {
 
     /** Calculates the number of cars produced for synnotch circuit. * */
     protected void synNotchCARCalculation() {
-        double n = 8;
+        double n = 4.4;
         int newCars =
                 (int) (maxCars / (1 + Math.pow(synNotchThreshold, n) / Math.pow(boundSynNotch, n)));
         cars = Math.max((int) (cars - (carDegradationConstant * cars * TAU)), newCars);

src/arcade/patch/agent/cell/PatchCellCARTCombinedInhibitory.java

@@ -90,7 +90,7 @@ protected void calculateCARS(MersenneTwisterFast random, Simulation sim) {
 
     /** Calculates the number of cars produced for receptor circuit. * */
     protected void receptorCars() {
-        double n = 8;
+        double n = 4.4;
         int removeCARs =
                 (int) (maxCars / (1 + Math.pow(boundSynNotch, n) / Math.pow(synNotchThreshold, n)));
         cars = Math.min(cars + (int) (basalCARGenerationRate * TAU), removeCARs);

src/arcade/patch/agent/module/PatchModuleCytotoxicity.java

@@ -9,6 +9,7 @@
 import arcade.patch.agent.cell.PatchCellCART;
 import arcade.patch.agent.cell.PatchCellTissue;
 import arcade.patch.agent.process.PatchProcessInflammation;
+import arcade.patch.env.location.PatchLocation;
 import arcade.patch.sim.PatchSimulation;
 import arcade.patch.util.PatchEnums.Domain;
 import arcade.patch.util.PatchEnums.State;
@@ -82,6 +83,8 @@ public void step(MersenneTwisterFast random, Simulation sim) {
                 eventData.put("tissue-cell-type", target.getPop());
                 eventData.put("type", "lysis");
                 eventData.put("timestamp", (int) ((PatchSimulation) sim).getSchedule().getTime());
+                eventData.put(
+                        "tissue-location", ((PatchLocation) target.getLocation()).getCoordinate());
                 patchSim.logEvent(eventData);
             }
         }

src/arcade/patch/agent/module/PatchModuleMigration.java

@@ -25,13 +25,17 @@ public class PatchModuleMigration extends PatchModule {
     /** Time required for cell migration [min]. */
     private final double movementDuration;
 
+    /** Boolean indicating if cell is on a matrigel. */
+    private final double matrigel;
+
     /**
      * Creates a migration {@link PatchModule} for the given cell.
      *
      * <p>Loaded parameters include:
      *
      * <ul>
      *   <li>{@code MIGRATION_RATE} = cell migration rate
+     *   <li>{@code MATRIGEL} = boolean indicating if cell is on a matrigel
      * </ul>
      *
      * @param cell the {@link PatchCell} the module is associated with
@@ -42,14 +46,15 @@ public PatchModuleMigration(PatchCell cell) {
         // Set loaded parameters.
         Parameters parameters = cell.getParameters();
         migrationRate = parameters.getDouble("migration/MIGRATION_RATE");
+        matrigel = parameters.getDouble("migration/MATRIGEL");
         movementDuration = Math.round(location.getCoordinateSize() / migrationRate);
     }
 
     @Override
     public void step(MersenneTwisterFast random, Simulation sim) {
         if (ticker > movementDuration) {
             PatchLocation newLocation = cell.selectBestLocation(sim, random);
-            if (newLocation == null) {
+            if (matrigel > 0 || newLocation == null) {
                 if (cell instanceof PatchCellCART) {
                     cell.setState(State.PAUSED);
                 } else {

src/arcade/patch/parameter.patch.xml

@@ -46,7 +46,7 @@
     <population id="BOUND_TIME" value="360" description="6 hours" />
 
      <!-- SynNotch specific parameters -->
-    <population id="SYNNOTCH_THRESHOLD" value="0.1" description="number threshold of total synnotch" />
+    <population id="SYNNOTCH_THRESHOLD" value="0.01" description="number threshold of total synnotch" />
     <population id="K_SYNNOTCH_ON" value="5.1E3" unit="Ms^-1" description="binding kinetic constant" />
     <population id="K_SYNNOTCH_OFF" value="9E-5" unit="s^-1" description="unbinding kinetic constant" />
     <population id="HILL_SYNNOTCH" value="4.4" description="hill coefficient for synnotch to CAR relationship" />
@@ -59,6 +59,7 @@
 
     <!-- migration module parameters -->
     <population.module module="migration" id="MIGRATION_RATE" value="0.24" unit="um/min" description="cell migration rate" />
+    <population.module module="migration" id="MATRIGEL" value="0" description="boolean indicating if cell is on a matrigel" />
 
     <!-- apoptosis module parameters -->
     <population.module module="apoptosis" id="DEATH_DURATION" value="1080" unit="min" description="time required for cell death" />