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Team:Paris Bettencourt/Modeling/Diffusion
From 2011.igem.org
Passive diffusion model
Introduction
Our first calculations of the diffusion of molecules inside a cell shows that the diffusion inside a cell is a very fast process (see the bottom of this page). It takes from 10 seconds to one minute for a component of the cell to have the average movement in the order of magnitude of the size of the cell. We wanted to explore further about the speed the passive diffusion can be achieved for a molecule to pass with passive diffusion, to see if the speed of molecule transfer through nanotubes is compatible with passive diffusion hypothesis.
We try to propose several ideas about the origin of the molecule transfer, to know if it is faster than the diffusion or imply more sophisticated models (see toward assisted diffusion). We also propose some experiments to verify these models.
The designs had been devised so that we can try to measure the speed of the diffusion through the tubes (see the Design & concepts page).
About the passive diffusion model
Earlier, we did some math to calculate the speed of the diffusion inside a cell. But we were in spherical coordinates, that is to say a mathematically friendly conditions. Here, we have to deal with a more complex geometry, so we had to be helped by a computer.
The essence of the model remains the same than the stochastic motion approach, but in this space we introduce boundary limits with the shape of two cells linked by a tube. We observe the passage of the molecules through the tube and we calculate the time taken for a molecule (like a transcription factor) to leave the emitter cell, diffuse though the tube and meet a target in the receiver cell.
Model description
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First we design a simple representation of the model with 2 boxes for cells and a tube between them. Each cell is designed like a 3D matrix(M*M*M) witch is proportional to the studied molecule. |
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We define the matrix size using our hypotesis about diffusion. So we create the cell matrix using this formula : 
We want to model each particle with a pixel, so each occupation site need to be 1px large. We calculate N, and with this formula, we obtain the model size M of our cell 
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For example : for glucose, if we want to have a size of 1*1*1 the matrix representing the cell needs to be 1000*1000*1000 and the nanotube which is 1/10 large of the cell will be 100*100*200.
We define the size of cells for each molecule of the hypothesis array :
We develop a java software to simulate this model (downloadable here). each simulation is done on 100 molecules in 10 rows. All the 100 molecules of the simulation will start in one cell and move randomly until at least 10 molecules pass through the nanotube to the other cell.
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We use a synchronous model so that all 100 molecules move simultaneously. At each row (step of execution), all the molecules move randomly from their site to one of the 26 other possible positions. |
this simulation takes into account :
- Movement of particle : each particle has a random movement at each row.
- collision with cell membrane, nanotube and self collision. We have 2 models of collision :
- Random restart model
- Wait and see model
Random restart
In this collision model, when a particle collides with another object, it is reset to a random position not occupied by another particle in the first cell. This model is stastistically correct because of the random definition of the particle movement. We can compare the teleportation of one particle to its degradation and synthesis of a new one.
Wait and see
In this collision model, when a particle collides with another object, it stays in place, waiting for the next row, so the molecule loses one movement, but it stays a credible model because of the random definition of the movement. This model has some problems due to the time lost by doing nothing with the particle. This model is actually only theoretic, the java program taking more than 2 hours to calculate the movement. This problem can be explained by the fact that particles keep colliding in the nanotube and stop other molecules which enter the nanotube by colliding with them.
How do we calculate the real time ?
A row corresponds to the movement from one site to another. The time it takes without boundary limitation is 
[1]
We obtain the real time of diffusion of 10 molecules through the nanotube with :
finally we obtain the time for diffusion from a cell to an other with :
For more accuracy, we do 10 simulations for each type of molecule, and we take the average time of those 10.
Maya modeling
This model is mapped in Maya for a user friendly aspect. This graphic representation is just for you to have an idea of diffusion and it doesn't use the diffusion equation used by the java program. In this representation, particles move linearly and are subjected to random turbulences.
Results
Results extracted from java have an output for 100 molecules and 10 rows. The average time for one molecule is calculated with the results 10 molecules passing from cell 1 to cell 2
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Conclusion
Looking at these results, it seems that speed diffusion is proportional to the square of particle size. Those times are really short, so we can't clearly define if it is active or passive diffusion. Because of the lack of experimental results, we can't compare modeling results to the actual time measured in vivo. This software can be extended for other molecules, but diffusion coefficient is an ambiguous information, and data differs from one publication to another, so simulating for a particular molecule is subject to error due to different definitions from a paper to an other.
References
- Diffusion-based Channel Characterization in Molecular Nanonetworks. Llatser, I., Alarcón, E. and Pierobon, M., to appear in Proc. of the 1st IEEE International Workshop on Molecular and Nano Scale Communication (MoNaCom), held in conjunction with IEEE INFOCOM, Shanghai (China), April 2011
