A Bio-energetic Modeling and Simulation of Myxobacteria...

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Introduction Off-Lattice Model Simulation Results Dynamic Energy Budget (DEB) Fruiting Body Formation A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle Björn Birnir Department of Mathematics and Center for Complex and Nonlinear Science University of California, Santa Barbara Notre Dame Oct. 1, 2008 Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyc

Transcript of A Bio-energetic Modeling and Simulation of Myxobacteria...

Page 1: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

A Bio-energetic Modeling and Simulation ofMyxobacteria Life-Cycle

Björn Birnir

Department of Mathematicsand

Center for Complex and Nonlinear ScienceUniversity of California, Santa Barbara

Notre Dame Oct. 1, 2008

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 2: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Graduate Student and Collaborators

The graduate student who is doing all the simulations is

Melisa HendrataWe also collaborate with an experimental group at UCLA,

Wenyuan Shi and his postodoc Renata Lux

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 3: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Outline

1 IntroductionBiological BackgroundLattice vs. Off-Lattice Model

2 Off-Lattice ModelModeling Cell CharacteristicsModeling Cell Motility and C-signaling

3 Simulation ResultsA and S-motilityC-signaling

4 Dynamic Energy Budget (DEB)

5 Fruiting Body Formation

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 4: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Biological BackgroundLattice vs. Off-Lattice Model

Cell Characteristics

Social behavior→ complex multicellular organizationMotility engines:

A(adventurous)-motility: slime secretionS(social)-motility: pili

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 5: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Biological BackgroundLattice vs. Off-Lattice Model

Cell Characteristics

Social behavior→ complex multicellular organizationMotility engines:

A(adventurous)-motility: slime secretionS(social)-motility: pili

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 6: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Biological BackgroundLattice vs. Off-Lattice Model

Cell Characteristics

Social behavior→ complex multicellular organizationMotility engines:

A(adventurous)-motility: slime secretionS(social)-motility: pili

(Ref: D. Kaiser, 2003)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 7: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Biological BackgroundLattice vs. Off-Lattice Model

Myxobacteria strains:Motile: A+S+ (wild-type), A+S-, A-S+Nonmotile: A-S-

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 8: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Biological BackgroundLattice vs. Off-Lattice Model

Myxobacteria life cycle

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 9: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Biological BackgroundLattice vs. Off-Lattice Model

Fruiting body formationnon-chemotaxiscontrolled by C-signal morphogendirect cell-cell local interaction

(Ref: S. Kim and D. Kaiser, 1990)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 10: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Biological BackgroundLattice vs. Off-Lattice Model

Lattice vs. Off-Lattice model

LGCA (Lattice Gas Cellular Automaton) modeluses hexagonal latticegeometric constraint

Off-Lattice modelfree movement in spacereduce geometric constraint

(Ref: Y. Wu et al., 2006)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 11: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Biological BackgroundLattice vs. Off-Lattice Model

Lattice vs. Off-Lattice model

LGCA (Lattice Gas Cellular Automaton) modeluses hexagonal latticegeometric constraint

Off-Lattice modelfree movement in spacereduce geometric constraint

(Ref: Y. Wu et al., 2006)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 12: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Modeling Cell CharacteristicsModeling Cell Motility and C-signaling

Cell Representation

string of 4 to 7 nodes, connected by segmentcell orientationpolarity reversal

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 13: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Modeling Cell CharacteristicsModeling Cell Motility and C-signaling

Cell Division

cell waits until it has fully grown before dividingcell divides in the middlelength of new cells is half of original cell

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 14: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Modeling Cell CharacteristicsModeling Cell Motility and C-signaling

General Assumptions

cell movement is directed by anterior nodecell moves with a fixed step lengthcollision handling mechanism: align or stop

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 15: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Modeling Cell CharacteristicsModeling Cell Motility and C-signaling

Modeling A-motility

searching circleturn at acute angle to follow slime trailneed to consider cell density

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 16: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Modeling Cell CharacteristicsModeling Cell Motility and C-signaling

Modeling S-motility

searching area around the anterior nodecell moves towards the most crowded quadrant

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 17: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Modeling Cell CharacteristicsModeling Cell Motility and C-signaling

Modeling C-signaling

C-signaling occurs when two cells are in end-to-endcontactcell turns to direction that increases the level of C-signalingC-signaling triggers locking between cellsN is number of C-signal molecules on the cell surface

dNdt

=cN(Nmax − N)

Nmax(1)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 18: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

A and S-motilityC-signaling

A+S+

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 19: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

A and S-motilityC-signaling

A-S+

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 20: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

A and S-motilityC-signaling

A+S-

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 21: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

A and S-motilityC-signaling

Comparison with Experiments

(Ref: C. Wolgemuth et al., 2002)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 22: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

A and S-motilityC-signaling

C-signaling

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 23: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Dynamic Energy Budget

describes how cells acquire and utilize energy formaintenance, growth and divisionuses κ-rule: a fixed fraction κ of energy flowing out ofreserves is used for maintenance and growth, and the restfor reproductiontrigger mechanism from the swarming stage to the stage offruiting body formation

(Ref: S. Kooijman, 2000)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 24: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

DEB Model

dLdt

=ν̇

3(E/Em)− (L/Lm)

g + (E/Em)(2)

dEdt

=Am

L

(f − E

Em

)(3)

wheref =

XK + X

, ν̇ =Am

Em, g =

GκEm

(4)

E = stored energy density, L = length, X = food density,

κ = fraction of utilized energy spent on maintenance and growth,

K = saturation coefficient, G = energy costs for a unit increase in size,

Em = max storage energy, Lm = max length, Am = max assimilation rate

(Ref: R. Nisbet et al. and S. Kooijman, 2000)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 25: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Non-dimensionalization

LetL∗ =

LLm

, E∗ =E

Em(5)

Then

dL∗

dt=

ν̇

3Lm

(E∗ − L∗)(g + E∗)

(6)

dE∗

dt=

ν̇

L∗Lm

(f − E∗

)(7)

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 26: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Experimental data:

Doubling time = 3 hours (∼ 900 time steps)

Cell length = 2-12 µm

Estimated parameters: f = 0.95, ν̇ = 0.25, g = 0.5

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 27: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Fruiting Body Formation

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 28: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Summary

A interacting particle model of myxobacteria simulates thedifferent swarming patterns of three strains of bacteriaA dynamic energy budget (DEB) model controls thereproduction (splitting) of the bacteria and triggers thetransition from swarming into the starvation phaseIn the starvation phase DEB, with the addition ofC-signaling, controls the different stages of the fruitingbody formations culminating in sporulation

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 29: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Summary

A interacting particle model of myxobacteria simulates thedifferent swarming patterns of three strains of bacteriaA dynamic energy budget (DEB) model controls thereproduction (splitting) of the bacteria and triggers thetransition from swarming into the starvation phaseIn the starvation phase DEB, with the addition ofC-signaling, controls the different stages of the fruitingbody formations culminating in sporulation

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 30: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Summary

A interacting particle model of myxobacteria simulates thedifferent swarming patterns of three strains of bacteriaA dynamic energy budget (DEB) model controls thereproduction (splitting) of the bacteria and triggers thetransition from swarming into the starvation phaseIn the starvation phase DEB, with the addition ofC-signaling, controls the different stages of the fruitingbody formations culminating in sporulation

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle

Page 31: A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cyclecnls.math.ucsb.edu/files/cnls/research-documents/myxo... · 2012. 11. 5. · A Bio-energetic Modeling and Simulation

IntroductionOff-Lattice Model

Simulation ResultsDynamic Energy Budget (DEB)

Fruiting Body Formation

Summary

A interacting particle model of myxobacteria simulates thedifferent swarming patterns of three strains of bacteriaA dynamic energy budget (DEB) model controls thereproduction (splitting) of the bacteria and triggers thetransition from swarming into the starvation phaseIn the starvation phase DEB, with the addition ofC-signaling, controls the different stages of the fruitingbody formations culminating in sporulation

Björn Birnir A Bio-energetic Modeling and Simulation of Myxobacteria Life-Cycle