Rodenfels2019 - Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling

  public model
Model Identifier
BIOMD0000000952
Short description
All living systems function out of equilibrium and exchange energy in the form of heat with their environment. Thus, heat flow can inform on the energetic costs of cellular processes, which are largely unknown. Here, we have repurposed an isothermal calorimeter to measure heat flow between developing zebrafish embryos and the surrounding medium. Heat flow increased over time with cell number. Unexpectedly, a prominent oscillatory component of the heat flow, with periods matching the synchronous early reductive cleavage divisions, persisted even when DNA synthesis and mitosis were blocked by inhibitors. Instead, the heat flow oscillations were driven by the phosphorylation and dephosphorylation reactions catalyzed by the cell-cycle oscillator, the biochemical network controlling mitotic entry and exit. We propose that the high energetic cost of cell-cycle signaling reflects the significant thermodynamic burden of imposing accurate and robust timing on cell proliferation during development.
Format
SBML (L2V4)
Related Publication
  • Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling.
  • Rodenfels J, Neugebauer KM, Howard J
  • Developmental cell , 3/ 2019 , Volume 48 , Issue 5 , pages: 646-658.e6 , PubMed ID: 30713074
  • Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. Electronic address: jonathan.rodenfels@gmail.com.
  • All living systems function out of equilibrium and exchange energy in the form of heat with their environment. Thus, heat flow can inform on the energetic costs of cellular processes, which are largely unknown. Here, we have repurposed an isothermal calorimeter to measure heat flow between developing zebrafish embryos and the surrounding medium. Heat flow increased over time with cell number. Unexpectedly, a prominent oscillatory component of the heat flow, with periods matching the synchronous early reductive cleavage divisions, persisted even when DNA synthesis and mitosis were blocked by inhibitors. Instead, the heat flow oscillations were driven by the phosphorylation and dephosphorylation reactions catalyzed by the cell-cycle oscillator, the biochemical network controlling mitotic entry and exit. We propose that the high energetic cost of cell-cycle signaling reflects the significant thermodynamic burden of imposing accurate and robust timing on cell proliferation during development.
Contributors
Submitter of the first revision: Ahmad Zyoud
Submitter of this revision: Ahmad Zyoud
Modellers: Ahmad Zyoud

Metadata information

is (3 statements)
BioModels Database MODEL2004170001
BioModels Database MODEL2004170001
BioModels Database BIOMD0000000952

isDescribedBy (1 statement)
PubMed 30713074

hasTaxon (1 statement)
Taxonomy Danio rerio

hasPart (1 statement)
Gene Ontology regulation of cell cycle

hasProperty (2 statements)
Mathematical Modelling Ontology Ordinary differential equation model
CHMO_0002076

isDerivedFrom (1 statement)

Curation status
Curated


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Model files

Rodenfels2019_V1.xml SBML L2V4 Rodenfels2019 - Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling 102.24 KB Preview | Download

Additional files

Rodenfels2019_V1.cps COPASI version 4.27 (Build 217) Rodenfels2019 - Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling_Fig.6B 160.31 KB Preview | Download
Rodenfels2019_V1.sedml sed-ml L1V2 Rodenfels2019 - Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling_Fig.6B 7.45 KB Preview | Download

  • Model originally submitted by : Ahmad Zyoud
  • Submitted: Apr 17, 2020 3:03:15 PM
  • Last Modified: May 14, 2020 7:44:07 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: May 14, 2020 7:44:07 PM
    • Submitted by: Ahmad Zyoud
    • With comment: Automatically added model identifier BIOMD0000000952
  • Version: 1 public model Download this version
    • Submitted on: Apr 17, 2020 3:03:15 PM
    • Submitted by: Ahmad Zyoud
    • With comment: Import of Rodenfels2019 - Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
S

C120264
60.0 mmol
PP2A

Q6NY64 ; protein-containing complex
60.0 mmol
Cyclin B1 Cdk1 complex phosphorylated

Q7ZU21 ; Q7T3L7 ; active ; protein-containing complex
60.0 mmol
Cyclin B1 Cdk1 complex total

Q7ZU21 ; Q7T3L7 ; protein-containing complex
60.0 mmol
Cyclin B1 Cdk1 complex unphosphorylated

Q7T3L7 ; Q7ZU21 ; protein-containing complex
0.0 mmol
SPPP2A

protein-containing complex
0.0 mmol
Q

heat generation
0.0 mmol
APC C active

Q561X1 ; active
0.0 mmol
Reactions
Reactions Rate Parameters
=> S; SCdk1, cdk1a, SPPP2A nuclear*((Kcdk_off*SCdk1-Kcdk_on*S*cdk1a)+Kcatpp2*SPPP2A) Kcatpp2 = 1800.0; Kcdk_off = 1.0; Kcdk_on = 10.0
=> PP2A; SPPP2A, SP nuclear*((Kpp2_off*SPPP2A+Kcatpp2*SPPP2A)-Kpp2_on*SP*PP2A) Kcatpp2 = 1800.0; Kpp2_off = 0.01; Kpp2_on = 100.0
Cyclin_B1_Cdk1_complex_phosphorylated => ; APC_C_active nuclear*k_dest*APC_C_active*Cyclin_B1_Cdk1_complex_phosphorylated k_dest = 0.76
Cyclin_B1_Cdk1_complex_total = Cyclin_B1_Cdk1_complex_unphosphorylated+Cyclin_B1_Cdk1_complex_phosphorylated [] []
Cyclin_B1_Cdk1_complex_unphosphorylated => ; APC_C_active nuclear*k_dest*APC_C_active*Cyclin_B1_Cdk1_complex_unphosphorylated k_dest = 0.76
Cyclin_B1_Cdk1_complex_unphosphorylated => Cyclin_B1_Cdk1_complex_phosphorylated nuclear*1/r^(1/2)*k_cdk1_on*(1+p/(1+(ec50_cdc25/Cyclin_B1_Cdk1_complex_phosphorylated)^n_cdc25))*Cyclin_B1_Cdk1_complex_unphosphorylated n_cdc25 = 11.0; r = 0.03125; k_cdk1_on = 0.06726; ec50_cdc25 = 30.0; p = 5.0
=> SPPP2A; SP, PP2A nuclear*((-(Kcatpp2+Kpp2_off))*SPPP2A+Kpp2_on*SP*PP2A) Kcatpp2 = 1800.0; Kpp2_off = 0.01; Kpp2_on = 100.0
Cyclin_B1_Cdk1_complex_phosphorylated => Cyclin_B1_Cdk1_complex_unphosphorylated nuclear*r^(1/2)*k_cdk1_off*(1+p/((Cyclin_B1_Cdk1_complex_phosphorylated/ec50_wee1)^n_wee1+1))*Cyclin_B1_Cdk1_complex_phosphorylated r = 0.03125; k_cdk1_off = 0.06726; n_wee1 = 3.5; p = 5.0; ec50_wee1 = 35.0
=> Q; SPPP2A, SP, PP2A nuclear*((-(Kcatpp2+Kpp2_off))*SPPP2A+Kpp2_on*SP*PP2A)*Embryo*delta_Hdesphos*Kcatpp2 delta_Hdesphos = 40000.0; Kcatpp2 = 1800.0; Kpp2_off = 0.01; Kpp2_on = 100.0
=> APC_C_active; Plx1_active, APC_C_total nuclear*k_apc_on/(1+(ec50_apc/Plx1_active)^n_apc)*(APC_C_total-APC_C_active) n_apc = 4.0; k_apc_on = 1.5; ec50_apc = 0.5
Curator's comment:
(added: 14 May 2020, 19:43:30, updated: 14 May 2020, 19:43:30)
Figure 6B has been reproduced by using COPASI 4.27 (Build 217) The embryo volume should be used in liters ( 60*10-6) rather than ┬Ám3 and the there was a typo in equation for the cdki. the sign has been changed to a - instead of + Furthermore, modification has been done to a few of the original Tsai et al. parameters by multiplication by a factor of 1.9 to match the zebrafish cell cycle