Team:Evry/Auxin diffusion

From 2012.igem.org

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<h2>Overview</h2>
<h2>Overview</h2>
<ul>
<ul>
-
Using PDE instead of ODE allows one to take into account the space dimensions. Where in the ODE model, the concentration of auxin in a compartment was considered homogeneous, here we can represent the variations internal to the compartment. When taking into account the space dimensions, new problems arise: finding a coherent geometry, 2D vs 3D model, precision, etc. We chose to model a slice of a tadpole's tail based on images from [ADD BOOK REF]. Putting multiple such slices one after the other allows us to approximate a 3 dimensions model.
+
Using PDE instead of ODE allows one to take into account the space dimensions. Where in the ODE model, the concentration of auxin in a compartment was considered homogeneous, here we can represent the variations in concentration in each compartment.We are then able to estimate delays between arrival in one end of a compartement and exit from the other end. When taking into account the space dimensions, new problems arise: finding a coherent geometry, 2D vs 3D model, precision, etc. We chose to model a slice of a tadpole's tail based on images. Adding multiple slices one after the other allows us to approach a 3 dimensions model.
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<h2>Hypothesis</h2>
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<h2>Assumptions</h2>
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+
-
There are the different hypothesis we were constrained to make in order to model the system:
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<ol>
<ol>
-
     <li>The quantity of auxins is homogeneous in the blood</li>
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     <li>The quantity of auxins is homogeneous in blood</li>
 +
    <li> Movement of auxins in skin isn't dependent on where the skin is; it is the same in skin around the head and in the one surrounding the tail.</li>
</ol>
</ol>
 +
<h2>Model description</h2>
<h2>Model description</h2>
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The diffusion equation is used to model the repartition of auxin's molecule when not subject to any flow (in the skin for example).
The diffusion equation is used to model the repartition of auxin's molecule when not subject to any flow (in the skin for example).
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The equation is states as follows:
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The equation is stated as follow:
<center>
<center>
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<ol>
<ol>
   <li>Skin</li>
   <li>Skin</li>
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   <li>Blood vessels or muscles (depending on the model)</li>
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   <li>Blood vessels</li>
   <li>Notochord</li>
   <li>Notochord</li>
   <li>Spinal cord</li>
   <li>Spinal cord</li>
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</center>
</center>
-
As seen on the picture above, the geometry is composed of very elementary shapes: circles and ellipses. Note that in the model, the shapes and positions of the different areas can be modified. In fact their are no really fixed geometry because it varies from tadpoles to tadpoles.
+
As seen on the picture above, the geometry is composed of very elementary shapes: circles and ellipses. Note that in the model, the shapes and positions of the different areas can be modified. In fact there is no really fixed geometry because it varies from a tadpole to another.
<h3>Limit conditions</h3>
<h3>Limit conditions</h3>
 +
 +
<h4>null Neumann condition</h4>
We consider in this model the tadpole as a closed system: no exchanges are allowed between the external medium and the skin. This hypothesis is modelized by using the neumann boundary condition with a value of 0:
We consider in this model the tadpole as a closed system: no exchanges are allowed between the external medium and the skin. This hypothesis is modelized by using the neumann boundary condition with a value of 0:
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</center>
</center>
-
<h2>Calibration</h2>
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This condition is also found at these other boundaries:
 +
<ol>
 +
  <li>blood <-> notochord</li>
 +
  <li>blood <-> spinal cord</li>
 +
</ol>
 +
 
 +
<h4>Exchange between different tissues</h4>
 +
 
 +
For the exchanges between other compartments, we use the same Neumann condition but modify the value of the right hand term.
 +
This values is now computed depending on the neighbors that do not belong to the same tissue.
 +
 
 +
<center>
 +
<img src="https://static.igem.org/mediawiki/2012/e/ef/Neumann-int.png" alt="neumann int" />
 +
</center>
 +
 
 +
where:
 +
 
 +
<ul>
 +
  <li>P<sub>x <-> y</sub> is the permeability between compartments x and y</li>
 +
  <li>neighbors is a function computing the 4-connexity neighborhood of a point</li>
 +
</ul>
 +
 
 +
<h3>Parameters</h3>
 +
 
 +
<center>
 +
<table id="param">
 +
  <tr>
 +
    <th>Description</th>
 +
    <th>Symbol</th>
 +
    <th>Type</th>
 +
    <th>Values</th>
 +
  </tr>
 +
 
 +
  <tr>
 +
    <td>Permeabilities</td>
 +
    <td>P</td>
 +
    <td>calculated</td>
 +
    <td><a href="https://2012.igem.org/Team:Evry/parameters#permeabilities">here</a></td>
 +
  </tr>
 +
 
 +
  <tr>
 +
    <td>Diffusion constants</td>
 +
    <td>D</td>
 +
    <td>calculated</td>
 +
    <td><a href="https://2012.igem.org/Team:Evry/parameters#surfaces">here</a></td>
 +
  </tr>
 +
 
 +
  <tr>
 +
    <td>Volumes</td>
 +
    <td>V</td>
 +
    <td>calculated</td>
 +
    <td><a href="https://2012.igem.org/Team:Evry/parameters#volumes">here</a></td>
 +
  </tr>
 +
 
 +
  <tr>
 +
    <td>Degradation rate</td>
 +
    <td>D<sub>die</sub>
 +
    <td>estimated</td>
 +
    <td>unknown</td>
 +
  </tr>
 +
 
 +
  <tr>
 +
    <td>Creation rate</td>
 +
    <td>D<sub>born</td>
 +
    <td>computed</td>
 +
    <td><a href="https://2012.igem.org/Team:Evry/plasmid_splitting">plasmid repartition model</a></td>
 +
  </tr>
 +
</table>
 +
</center>
<h2>Results</h2>
<h2>Results</h2>
 +
<p>The program implemented on Netlogo gives us the folowing results:</p>
 +
 +
<center>
 +
<img src="https://static.igem.org/mediawiki/2012/7/73/Anim.gif">
 +
</center>
 +
 +
<p> The coloration of every patch of skin and capillaries is proportional to its concentration in auxin. We can see here the diffusion process from the skin to the vessels. The on the top right corner reflects the variation of the quantity of auxin in skin. We can see that this variation corresponds to the results of the ODE model for the same initial conditions (0 concentration in water that is surrounding the tadpole and non-zero quantity of auxin in skin.</p>
 +
<p>
 +
 +
<h2>Building back the global solution</h2>
 +
 +
Once the concentrations of auxins in the different tissues have been obtained in one slice, we must integrate these results. We use slices with constant length to simplify the problem, so every slice has a length of dz. To take better into account the areas of interest, we could also imagine having slices of different sizes depending on the activity of the area.<br/><br/>
 +
 +
The integration scheme for slices of constant size is the following:
 +
 +
<center>
 +
  <img src="https://static.igem.org/mediawiki/2012/6/63/Integration-pde.png" alt="integration scheme for pde"/>
 +
</center>
 +
 +
Which in the implementation simply become a sum over all the slices:
 +
 +
<center>
 +
  <img src="https://static.igem.org/mediawiki/2012/2/2b/Summation-pde.png" alt="summation scheme for pde" />
 +
</center>
<h2>Conclusion</h2>
<h2>Conclusion</h2>
 +
<p>This model has the qualitatively the same results as the ODE model, which confirms the types of equations we had used for that global model. It has much more parameters, which would be very difficult to determine. Nevertheless we are able to visualise the diffusion through each patch. </p>
 +
 +
<h2>Downloading the model</h2>
 +
 +
You can find the model as a zip tarball <a href="https://static.igem.org/mediawiki/2012/6/6e/Transport-model-pde.zip">here</a>.<br/><br/>
-
<h2>References</h2>
+
It has been developed under Netlogo 5.0.1. To use it, just launch NetLogo and open the "tad.nlogo" file. The use of NetLogo is very intuitive.
<div id="citation_box">
<div id="citation_box">

Latest revision as of 03:22, 27 October 2012

Model using Partial Differential Equations(PDE)

Overview

    Using PDE instead of ODE allows one to take into account the space dimensions. Where in the ODE model, the concentration of auxin in a compartment was considered homogeneous, here we can represent the variations in concentration in each compartment.We are then able to estimate delays between arrival in one end of a compartement and exit from the other end. When taking into account the space dimensions, new problems arise: finding a coherent geometry, 2D vs 3D model, precision, etc. We chose to model a slice of a tadpole's tail based on images. Adding multiple slices one after the other allows us to approach a 3 dimensions model.

    Assumptions

    1. The quantity of auxins is homogeneous in blood
    2. Movement of auxins in skin isn't dependent on where the skin is; it is the same in skin around the head and in the one surrounding the tail.

    Model description

    The PDE model is similar to the ODE one except that it takes into account the geometry. This allows us to model more complex phenomenon such as diffusion and transport.

    Equations

    The diffusion equation is used to model the repartition of auxin's molecule when not subject to any flow (in the skin for example). The equation is stated as follow:
    diffusion equation
    where:
    • x = (x1, x2) is a 2 dimensional vector
    • c is a function representing the auxin concentration
    • D is the diffusion constant
    • Δ is the Laplacian operator

    Geometry

    To keep the complexity of the numerical simulations low, we had to simplify the considered geometry. Hence, the slide of tadpole only contains the following elements:
    1. Skin
    2. Blood vessels
    3. Notochord
    4. Spinal cord
    5. Aorta
    6. Veins: caudal and dorsal
    tadpole geometry
    As seen on the picture above, the geometry is composed of very elementary shapes: circles and ellipses. Note that in the model, the shapes and positions of the different areas can be modified. In fact there is no really fixed geometry because it varies from a tadpole to another.

    Limit conditions

    null Neumann condition

    We consider in this model the tadpole as a closed system: no exchanges are allowed between the external medium and the skin. This hypothesis is modelized by using the neumann boundary condition with a value of 0:
    neumann ext
    This condition is also found at these other boundaries:
    1. blood <-> notochord
    2. blood <-> spinal cord

    Exchange between different tissues

    For the exchanges between other compartments, we use the same Neumann condition but modify the value of the right hand term. This values is now computed depending on the neighbors that do not belong to the same tissue.
    neumann int
    where:
    • Px <-> y is the permeability between compartments x and y
    • neighbors is a function computing the 4-connexity neighborhood of a point

    Parameters

    Description Symbol Type Values
    Permeabilities P calculated here
    Diffusion constants D calculated here
    Volumes V calculated here
    Degradation rate Ddie estimated unknown
    Creation rate Dborn computed plasmid repartition model

    Results

    The program implemented on Netlogo gives us the folowing results:

    The coloration of every patch of skin and capillaries is proportional to its concentration in auxin. We can see here the diffusion process from the skin to the vessels. The on the top right corner reflects the variation of the quantity of auxin in skin. We can see that this variation corresponds to the results of the ODE model for the same initial conditions (0 concentration in water that is surrounding the tadpole and non-zero quantity of auxin in skin.

    Building back the global solution

    Once the concentrations of auxins in the different tissues have been obtained in one slice, we must integrate these results. We use slices with constant length to simplify the problem, so every slice has a length of dz. To take better into account the areas of interest, we could also imagine having slices of different sizes depending on the activity of the area.

    The integration scheme for slices of constant size is the following:
    integration scheme for pde
    Which in the implementation simply become a sum over all the slices:
    summation scheme for pde

    Conclusion

    This model has the qualitatively the same results as the ODE model, which confirms the types of equations we had used for that global model. It has much more parameters, which would be very difficult to determine. Nevertheless we are able to visualise the diffusion through each patch.

    Downloading the model

    You can find the model as a zip tarball here.

    It has been developed under Netlogo 5.0.1. To use it, just launch NetLogo and open the "tad.nlogo" file. The use of NetLogo is very intuitive.

    References:

    1. Atlas of xenopus development,G. Bernardini, Springer, 1999.

    Retrieved from "http://2012.igem.org/Team:Evry/Auxin_diffusion"