Team:Evry/ODE model

From 2012.igem.org

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     <th>Type</th>
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     <td>calculated</td>
     <td>calculated</td>
     <td><a href="http://2012.igem.org/Team:Evry/parameters#permeabilities">here</a></td>
     <td><a href="http://2012.igem.org/Team:Evry/parameters#permeabilities">here</a></td>
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    <td><a href="http://2012.igem.org/Team:Evry/Experimentals_Parameters#2">link</a></td>
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     <td>calculated</td>
     <td>calculated</td>
     <td><a href="http://2012.igem.org/Team:Evry/parameters#surfaces">here</a></td>
     <td><a href="http://2012.igem.org/Team:Evry/parameters#surfaces">here</a></td>
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     <td>calculated</td>
     <td>calculated</td>
     <td><a href="http://2012.igem.org/Team:Evry/parameters#volumes">here</a></td>
     <td><a href="http://2012.igem.org/Team:Evry/parameters#volumes">here</a></td>
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     <td>unknown</td>
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    <td><a href="http://2012.igem.org/Team:Evry/Experimentals_Parameters#4">link</a></td>
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Revision as of 00:31, 27 September 2012

Model using Ordinary Differential Equations (ODE)

Overview

    This global model represents the tadpole as a three compartment system:
    1. The skin that produces (or receives) auxins, denoted S in the equations;
    2. The blood that transport auxins to the organs, denoted B;
    3. The organs (called receptors) that interacts with auxin molecules, denoted R.

    The parallel with an electric circuit is straightforward: the skin represents a generator that will propagate intensity to the other systems compartments; The blood represents wires, that convey this quantity throughout the system and interfaces are like resistors; Finally the organs are the sinks that use this intensity to work.

    Using this very idealized view of the tadpoles makes it possible to model it simply : The processes happening in the system can be approximated using Ordinary Differential Equations (ODE), one of the simplest form of differential equations; Plus, the organs repartition and shape are not taken into account. As showed in this page, these equations can be seen as approximations of more realistic PDEs where space considerations have been removed.

    Although our model is very general and simple, it allows to have a quantitative view. As many parameters would require much experiment to be estimated correctly. At this stage this quantitative model only allows us to make some prediction about the global behaviour of the system and gives us hints about the reasons for the success or failure of experiments.


    tadpole compartments

    Assumptions

    There are the different assumptions we were constrained to make in order to model the system:
    1. The auxin concentration inside a compartment is homogeneous
    2. This condition is inherent to this kind of modeling.
    3. No auxins can go from the skin directly to the organs.
    4. We have chosen to neglect the exchanges between the skin and the other organs.
    5. The auxin flow follows the concentration gradient between compartments.
    6. This assumption is based on the fact that a small capillary is nothing more than a hole in a cell layer. So the exchanges between the surrounding cells and the capillary are mutual.

    Model description

    Equations

    Each compartment is modeled by a differential equation representing the evolution of the auxin quantity as a function of the time. Each equations are composed of two kinds of terms: creation and degradation. The creation term can represent either a creation of auxin in the compartment or an arriving quantity of auxin from another one. In the same way, the degradation term can either represent a natural degradation of molecules or a quantity leaving the compartment.

    ODE system

    In this system,Ddie is a degradation rate, the other D terms represent the flows between the different compartments. We made them depend on the concentrations of both the in and out compartments as explained in assumption 2. Their mathematical formulation is the following:

    mathematical expression of debits

    Where:
    • S in m2, represents the area of the exchange surface between the two compartments.
    • P in m2, represents the permeability of the membrane between the specified compartments.
    • C in [quantity] / m3, represents the concentration of auxin in the specified compartment

    These flow equations are based on Newton's law of cooling where the difference between the concentrations of the two compartments gives the direction and magnitude of the flow. This allows us to model in a single equations the two opposite flows between the compartments.


    Parameters


    The parameters of the model are hard to estimate because direct experiences concerning auxin's behaviour in the xenopus where never made before, as it is a plant hormone.Moreover,the parameters are an aggregation of different physical values. This is due to the high level view provided by the model. The different parameters are:



    Description Symbol Type Values Experiment Proposition
    Permeabilities P calculated here link
    Contact surfaces S calculated here
    Volumes V calculated here
    Degradation rate Ddie estimated unknown link
    Creation rate Dborn computed plasmid repartition model

    Sensitivity Analysis

    There are 2 kinds of parameters in this model; those concerning the geometry of the tadpole and those concerning the behaviour of auxin in the tadpole's tissues. As auxin is a plant hormone, we had to evaluate these parameters by taking those of similar molecules. That's why the uncertainties on these measures are very big. For this category, we observed variations from reference value ref*10-3 to ref*103. You can see the effect of these variations:

    • For permeabilities:
    • For die rate:
    For the geometrical parameters, we observed variations going from ref*0.3 to ref*2.We've obtained:
    • For Surfaces:
    • For Volumes:

    Results

    By modifying the initial conditions and cw we have observed globaly 3 different behaviours of the system:
    • This first graph is obtained considering no auxin in the tadpole and cw=5.10-3mol.L-1 which is the concentration we wanted to use for experiences. The result shows that the quantity of auxin in skin and in the receptor grow until a limit value.It seems that we can make an electrical analogy; both skin and receptor behave as condensators that are charging.

    • If there has been injected auxin in the receptor and in skin: ns(t=0)=10 mmol nr(t=0)=10 mmol, we can observe a decrease of auxin in receptor before an establishement of the equilibrium. To continue the electrical analogy, we see that the receptor behaves as a condenser that is decharging , whereas skin is a charging condenser.

    • Here , the concentration in water has been devided by ten cw=0.5.10-3mol.L-1, while the initial value of skin is still ns(t=0)=10 mmol. We observe first a big increase in the receptor due to the diffusion of the auxin intially injected in skin then a decrease because of the small water concentration in auxin.

    • Conclusion

      This model being simplified to the maximum, has let us, thanks to an estimation of very few parameters, to see the global behaviour of the system. It helps us to determine expected behaviours and helps us to establish possible reasons of dysfunctions. Nevertheless, quantitatively, this model is too imprecise because it doesn't take tadpole's geomoetry into account. This is the aim of our most elaborated model which will use partial equations.

      References

      References:

      Other possible topologies

      With auxin in the external medium:
      tadpole + external compartments

      With a specific receptor organ:
      tadpole + other compartments