<?xml version='1.0' encoding='UTF-8'?> <MorpheusModel version="4"> <Description> <Details>Full title: Spatio-temporal model of YAP signaling in hepatocytes after partial hepatectomy. Date: 28.6.2018 Author: lutz.brusch@tu-dresden.de Software: Morpheus (open-source), download from https://morpheus.gitlab.io Reference: This model is described in the peer-reviewed publication "Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration" by Kirstin Meyer, Hernan Morales-Navarrete, Sarah Seifert, Michaela Wilsch-Braeuninger, Uta Dahmen, Elly M. Tanaka, Lutz Brusch, Yannis Kalaidzidis and Marino Zerial. Molecular Systems Biology 16:e8985, 2020. https://doi.org/10.15252/msb.20198985 </Details> <Title>YAP signaling</Title> </Description> <Space> <Lattice class="square"> <Neighborhood> <Order>1</Order> </Neighborhood> <Size symbol="size" value="30, 3, 0"/> </Lattice> <SpaceSymbol symbol="space"/> </Space> <Time> <StartTime value="0"/> <StopTime symbol="stop" value="5"/> <TimeSymbol symbol="time"/> </Time> <CellTypes> <CellType class="biological" name="Hepatocyte"> <Constant symbol="N" value="860" name="nucleus volume in square micron"/> <Constant symbol="C" value="5450" name="cytoplasm volume in square micron"/> <Property symbol="SENSOR" value="0.245*C" name="amount of SENSOR"/> <Property symbol="inact_SENSOR" value="5.255*C" name="amount of inactive SENSOR"/> <Property symbol="YAP" value="1*C" name="amount of YAP"/> <Property symbol="inact_YAP" value="0*C" name="amount of inactive YAP"/> <Property symbol="inact_YAP_SF" value="0*C" name="amount of inactive YAP bound to SF"/> <Property symbol="N_YAP" value="1" name="concentration of nuclear YAP"/> <System solver="adaptive45" time-scaling="1000"> <DiffEqn symbol-ref="SENSOR"> <Expression>- C * Michaelis_Menten(SENSOR / C, Km, V) + C * Michaelis_Menten(inact_SENSOR / C, Km_1, Tension)</Expression> </DiffEqn> <DiffEqn symbol-ref="inact_SENSOR"> <Expression>C * Michaelis_Menten(SENSOR / C, Km, V) - C * Michaelis_Menten(inact_SENSOR / C, Km_1, Tension)</Expression> </DiffEqn> <DiffEqn symbol-ref="YAP"> <Expression>k5 * inact_YAP - k4 * YAP * inact_SENSOR / C - k10 * YAP - k9 * YAP + k8 * N_YAP * N + C * k3_0 * s</Expression> </DiffEqn> <DiffEqn symbol-ref="inact_YAP"> <Expression>- k11 * inact_YAP - k5 * inact_YAP + k4 * YAP * inact_SENSOR / C - k6 * inact_YAP + k7 * inact_YAP_SF</Expression> </DiffEqn> <DiffEqn symbol-ref="inact_YAP_SF"> <Expression>k6 * inact_YAP - k7 * inact_YAP_SF</Expression> </DiffEqn> <DiffEqn symbol-ref="N_YAP"> <Expression>k9 * YAP / N - k8 * N_YAP</Expression> </DiffEqn> </System> <Property symbol="Tension" value="1"/> <Event trigger="on change" time-step="0.05" name="Tension for time t closer to 0.8d than to other measurements"> <Condition>time>0.4</Condition> <Rule symbol-ref="Tension"> <Expression>if(cell.id==1,1.8279930944312834, if(cell.id==2,1.7866460754759526, if(cell.id==3,1.8374519069180288, if(cell.id==4,1.8640351995565263, if(cell.id==5,1.8706834857072998, if(cell.id==6,1.8941858816263410, if(cell.id==7,1.8511397598872272, if(cell.id==8,1.9135216039396319, if(cell.id==9,1.9145071129239710, if(cell.id==10,1.8153404444156003, 1))))))))))</Expression> </Rule> </Event> <Event trigger="on change" time-step="0.05" name="Tension for time t closer to 1.5d than to other measurements"> <Condition>time>1.15</Condition> <Rule symbol-ref="Tension"> <Expression>if(cell.id==1,1.9807223334150590, if(cell.id==2,1.9130780850583866, if(cell.id==3,1.9643577716468286, if(cell.id==4,2.0020827404251120, if(cell.id==5,2.0252154507264140, if(cell.id==6,2.0703197134079440, if(cell.id==7,1.9915999174723278, if(cell.id==8,2.0046213799240973, if(cell.id==9,1.9540901073551358, if(cell.id==10,1.8753435897018356, 1))))))))))</Expression> </Rule> </Event> <Event trigger="on change" time-step="0.05" name="Tension for time t closer to 2.0d than to other measurements"> <Condition>time>1.75</Condition> <Rule symbol-ref="Tension"> <Expression>if(cell.id==1,2.0217009184038360, if(cell.id==2,1.9258181971655592, if(cell.id==3,1.9518589890960070, if(cell.id==4,1.9123363331127760, if(cell.id==5,2.0319328550271623, if(cell.id==6,2.0158606286091496, if(cell.id==7,1.9434430184290816, if(cell.id==8,1.8907841188362082, if(cell.id==9,1.9473574849407167, if(cell.id==10,1.8715472190966007, 1))))))))))</Expression> </Rule> </Event> <Event trigger="on change" time-step="0.05" name="Tension for time t closer to 3.0d than to other measurements"> <Condition>time>2.5</Condition> <Rule symbol-ref="Tension"> <Expression>if(cell.id==1,1.8597267890032976, if(cell.id==2,1.7814702267887177, if(cell.id==3,1.8292379408251978, if(cell.id==4,1.8488155708410638, if(cell.id==5,1.8536661678277864, if(cell.id==6,1.8836145987139055, if(cell.id==7,1.8442276337980785, if(cell.id==8,1.8136740374044704, if(cell.id==9,1.8868282103886570, if(cell.id==10,1.8015329680486330, 1))))))))))</Expression> </Rule> </Event> <Event trigger="on change" time-step="0.05" name="Tension for time t closer to 5.0d than to other measurements"> <Condition>time>4.0</Condition> <Rule symbol-ref="Tension"> <Expression>if(cell.id==1,1.9088767623308390, if(cell.id==2,1.8488496952244589, if(cell.id==3,1.8616629446112190, if(cell.id==4,1.8244687794620162, if(cell.id==5,1.8557929833228486, if(cell.id==6,1.8447542721681303, if(cell.id==7,1.7726695922335742, if(cell.id==8,1.7074409071843903, if(cell.id==9,1.7730171801027250, if(cell.id==10,1.7408530847107613, 1))))))))))</Expression> </Rule> </Event> <Property symbol="s" value="if(cell.id==1,1.246692,
if(cell.id==2,1.383782,
if(cell.id==3,1.460713,
if(cell.id==4,1.516818,
if(cell.id==5,1.546580,
if(cell.id==6,1.650898,
if(cell.id==7,1.662168,
if(cell.id==8,1.613539,
if(cell.id==9,1.554600,
if(cell.id==10,1.324019,
1))))))))))" name="zonated (i.e. cell-dependent) YAP synthesis level"/> <Function symbol="Michaelis_Menten" name="Henri-Michaelis-Menten kinetics (irreversible)"> <Parameter symbol="substrate"/> <Parameter symbol="Km"/> <Parameter symbol="V"/> <Expression>V * substrate / (Km + substrate)</Expression> </Function> <Constant symbol="Km" value="0.25" name="Km"/> <Constant symbol="V" value="2.02" name="Vmax"/> <Constant symbol="Km_1" value="0.0008" name="Km"/> <Constant symbol="k3_0" value="1.7" name="k3,0 YAP synthesis rate factor"/> <Constant symbol="k4" value="0.19" name="YAP inactivation rate"/> <Constant symbol="k5" value="1" name="YAP activation rate"/> <Constant symbol="k6" value="0.18" name="inact_YAP binding to SF"/> <Constant symbol="k7" value="1" name="inact_YAP unbinding from SF"/> <Constant symbol="k8" value="1" name="nuclear export"/> <Constant symbol="k9" value="0.17" name="nuclear import"/> <Constant symbol="k10" value="1.8" name="YAP degradation"/> <Constant symbol="k11" value="30" name="inact_YAP degradation rate"/> <Property symbol="C_YAP_total" value="(YAP + inact_YAP + inact_YAP_SF) / C" name="total cytosolic YAP (t=0)"/> <Equation symbol-ref="C_YAP_total" name="total cytosolic YAP"> <Expression>(YAP + inact_YAP + inact_YAP_SF) / C</Expression> </Equation> <Property symbol="YAP_total" value="(C * C_YAP_total + N * N_YAP) / (C + N)" name="total cellular YAP"/> <Equation symbol-ref="YAP_total" name="total cellular YAP"> <Expression>(C * C_YAP_total + N * N_YAP) / (C + N)</Expression> </Equation> </CellType> </CellTypes> <CellPopulations> <Population size="10" type="Hepatocyte"> <InitCellObjects mode="distance"> <Arrangement repetitions="10, 1, 1" displacements="3, 0, 0"> <Box size="3.0, 3.0, 1.0" origin="0.0, 0.0, 0.0"/> </Arrangement> </InitCellObjects> </Population> </CellPopulations> <Analysis> <Gnuplotter time-step="0.05" decorate="true"> <Terminal name="png"/> <Plot title="nuclear YAP(x,t)"> <Cells value="N_YAP" min="0.9" max="1.7"/> </Plot> <Plot title="total YAP(x,t)"> <Cells value="YAP_total" min="0.9" max="1.7"/> </Plot> </Gnuplotter> <Logger time-step="0.8"> <Input> <Symbol symbol-ref="Tension"/> <Symbol symbol-ref="N_YAP"/> <Symbol symbol-ref="YAP_total"/> </Input> <Output> <TextOutput file-numbering="time" file-separation="time"/> </Output> <Plots> <Plot title="Fig.S9a: Tension(x,t)" file-numbering="time" time-step="0.8"> <Style style="lines"/> <Terminal terminal="png"/> <X-axis> <Symbol symbol-ref="cell.id"/> </X-axis> <Y-axis minimum="0.9" maximum="2.5"> <Symbol symbol-ref="Tension"/> </Y-axis> </Plot> <Plot title="Fig.S9c: nuclear YAP(x,t)" file-numbering="time" time-step="0.1"> <Style style="lines"/> <Terminal terminal="png"/> <X-axis> <Symbol symbol-ref="cell.id"/> </X-axis> <Y-axis minimum="0.0" maximum="2.0"> <Symbol symbol-ref="N_YAP"/> </Y-axis> </Plot> <Plot title="Fig.S9d: total cellular YAP(x,t)" file-numbering="time" time-step="0.1"> <Style style="lines"/> <Terminal terminal="png"/> <X-axis> <Symbol symbol-ref="cell.id"/> </X-axis> <Y-axis minimum="0.0" maximum="2.0"> <Symbol symbol-ref="YAP_total"/> </Y-axis> </Plot> </Plots> <Restriction> <Celltype celltype="Hepatocyte"/> </Restriction> </Logger> </Analysis> </MorpheusModel>