Team:Paris Bettencourt/Modeling/Assisted diffusion

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<h1>Assisted diffusion</h1>
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== Introduction to the model ==
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<h2>Introduction to the model</h2>
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The diffusion through the nanotubes is a fast process. This speed can be partially explained by the passive diffusion through the tubes. But what if it is faster?
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<table>
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The article from Dubey and Ben-Yehuda suggests that the diffusion is an active process. Several points can be opposed to this statement:
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<tr>
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* First, the diffusion is happening with molecule of different natures, that have nothing to do with the natural compoments of a cell
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<td>
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* Unlike the mamalian cells, the tube seems to have no "railroad" design for such a transport
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<img style="width:150px; margin-top:20px;" src="https://static.igem.org/mediawiki/2011/b/b9/Active-diff-button.png">
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</td>
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<td>
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<p> Inspired by the experiments of Dubey and Ben-Yehuda we asked ourselves several questions.  
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The question is: can we immagine a process that is faster than passive diffusion but does not rely on specific interractions?
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What kind of process could do this molecular transfer? How can we characterize it?
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The answer is probably yes, and in this page we propose a new model, really challenging for the mind, but that can play a role in the diffussion process through the nanotubes.
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It could be an active process, a passive diffusion or something else.
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== General physical concepts and Hypothesis ==
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Several arguments can be opposed to the <em>active process</em> hypothesis:
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<ul>
 +
<li>During the process, an exchange of <em>molecules of different natures</em> takes place. These molecules have nothing to do with the natural components of a cell (GFP, calcein, etc.). Thus there is <em>no specificity</em> of transport, and there should be no specific mechanism of active transport.</li>
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<li>Unlike the mammalian cells, the bacterial tubes seem to have no "railroad" to guide the transported molecules.</li>
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</ul>
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&nbsp; &nbsp; &nbsp; &nbsp;
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</td>
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<td>
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</table>
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<p>The question is :</p>
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<p><center><b>Can we develop a theoretical model of "active" transfer that can justify what was observed in the orignal article?</p>
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</b></center>
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=== Starting from an analogy ===
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<p>We need to know if such a model can be designed starting from physical laws and if this model can explain quantitatively the transfer through the nanotubes. Due to its purely physical nature, our model can also shed some light as to the nanotube formation.</p>
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Immagine two bottles of gaz connected by a tube. The fist one have an higher pressure than the second one. In the first one, diluted in the gaz, there are a few molecules of another nature, we follow the destiny.
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<p>We managed to come up with an idea for such a process, and in this page <em>we propose a new model</em> that can possibly explain the speed of the molecule exchange through the nanotubes.</p>
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When you open the tape, the bottle with a higher pressure will equillibrate with the other one my moving a certain quantity of it's molecules through the tube in the direction of the second bottle. These moving molecules will drag with them the copoment diluted in the gaz and a few of these molecules will be transported to the other bottle.
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<p>As a matter of fact, <em> the difference in membrane tension</em> between two bacteria could lead to a pressure difference. That could induce a small cytoplasmic transfer to reach internal pressure equilibrium. </p>
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<h2>Summary</h2>
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=== From the analogy to the biology ===
 
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Of cource, the cell is not a bag of liquid under pressure. The water is equillibrated at both sides of the exterior membrane. the pressure we are dealing with is not water or osmotic pressure (that is a "passive diffusion thermodynamical pressure"). There is a part of the cell we do not immediately think about that can undergo a huge variablilty of pressure: the membrane!
 
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Let's evaluate the constraints that the membrane underdo. First, as it is a gramm positive bacteria, the external sugar envelopp impose the shape of the bacteria. On the other hand, the osmotic pressure is pushing the membrane against the sugar wall. Inside the membrane, the number of phospho-lipids is fixed by the state of division on the cell.
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<div id="assisted_diff" style="margin-left:50px;">
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<div class="assisted_diff_link" style="position:relative; left:80px; top:30px;"><a href="https://2011.igem.org/Team:Paris_Bettencourt/Modeling/Assisted_diffusion/Membrane_tension"><img src="https://static.igem.org/mediawiki/2011/7/7b/Select_bilayer.png" /></a></div>
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<div class="assisted_diff_link" style="position:relative; left:375px; top:19px;"><a href="https://2011.igem.org/Team:Paris_Bettencourt/Modeling/Assisted_diffusion/Tube_formation"><img src="https://static.igem.org/mediawiki/2011/8/8f/Select_formation.png" /></a></div>
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<div class="assisted_diff_link" style="position:relative; left:339px; top:94px;"><a href="https://2011.igem.org/Team:Paris_Bettencourt/Modeling/Assisted_diffusion/From_membrane_tension_to_liquid_flux"><img src="https://static.igem.org/mediawiki/2011/4/47/Select_pressure.png" /></a></div>
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</div>
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<center><h4>Click on the circles on the above picture to discover our assisted diffusion model in details</h4></center>
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Though, a phospholipid is somehow behaving as a gaz trapped in a bottle. The ospotic pressure and the sugar layer are the bottle, and the number of particle trapped is giving thhe pression. This variation of pression can be important if the cell has just devide or if the cell is about to devide.
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<p>
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Model description in few words :
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</p>
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When the cell enter of communication, a flow of molecule can pass from the cell that have the highest membrane pressure to the other one. This is happening, when phospholipids are running around the tube.
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<p>
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But the tube is small and water has its own viscosity. If the pipe is moving, the water inside willfollow, with a Poiseuil shape sliding. Constituents diluted in water will move from one cell to another unidirectionally and faster than simply diffusing. This is a fast process that we have named after the "active" and "passive" diffusion, the "assisted diffusion"
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We do not know what is the mechanism behind nanotube formation. We can suppose they are made of lipid membrane within a cell-wall like matrix, as suggested by the original electron microscopy experiment. When the membrane of the two cells fuse, there might be a <em>difference of tension between the two phospholipid bilayers</em>. This phenomenon might lead to a <em>movement of lipids</em> from one membrane to the other. The newly arrived phospholipids change the membrane tension of the bacterium. As a consequence, they change the internal Laplace pressure <i>ΔP<sub>Lap</sub></i> of the bacterium.
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</p>
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=== When membranes behave like a 2D classical gaz ===
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<p>
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<center>
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<img src='https://static.igem.org/mediawiki/2011/7/7d/Laplacian_pressure.png' style="height:45px">
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</center>
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</p>
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== Calculating the membrane tension ==
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<p>
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where τ is membrane tension, R is a radius of bacterium.
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</p>
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== Back to the classical physics ==
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<p>
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A simple analogy of clothesline can help to understand what is happening. You need to pull more your clothesline to put more clothes on it. When you pull the rope by two ends you create a tension. The bigger the tension, the more weight (pressure) you can put on the rope.
 +
</p>
 +
 
 +
<p>
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All of this will lead to establishing the pressure difference at the tube extremities and we will get a Poiseuille's flow. Constituents diluted in water will move from one cell to another unidirectionally and faster than by simple diffusion. This is a fast process that we have named the <em>"assisted diffusion"</em>.
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</p>
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<div style="margin-left:50px; margin-right:50px; padding: 5px; border:2px solid black;"><b><p>The assisted diffusion model in 3 bullet points:
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<ul>
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    <li>Characteristic time of the process is about 100 ns</li>
 +
    <li>The effect strongly depends on the initial phospholipid distribution on the membrane of two connected bacteria</li>
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    <li>The phenomenon predicts the flux of only 0.1 % of the cytoplasme, not enough to explain the GFP experiment of the original paper</li>
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</ul></p></b></div>
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<html>
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<p>
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We have done a <a href='https://2011.igem.org/Team:Paris_Bettencourt/Modeling/Assisted_diffusion/Back_of_the_envelope_calculation'>back of the envelope calculation</a> to see whether an order of magnitude is acceptable.</p>
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<div id="citation_box">
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<p id="references">References</p>
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<ol>
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<li><i>Intercellular Nanotubes Mediate Bacterial Communication</i>, Dubey and Ben-Yehuda, Cell, 2011, available <a href="http://bms.ucsf.edu/sites/ucsf-bms.ixm.ca/files/marjordan_06022011.pdf">here</a></li>
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<li><i>BioNumbers</i> <a href="http://bionumbers.hms.harvard.edu/">here</a></li>
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</ol>
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Latest revision as of 02:14, 29 October 2011

Team IGEM Paris 2011

Assisted diffusion

Introduction to the model

Inspired by the experiments of Dubey and Ben-Yehuda we asked ourselves several questions. What kind of process could do this molecular transfer? How can we characterize it? It could be an active process, a passive diffusion or something else. Several arguments can be opposed to the active process hypothesis:

  • During the process, an exchange of molecules of different natures takes place. These molecules have nothing to do with the natural components of a cell (GFP, calcein, etc.). Thus there is no specificity of transport, and there should be no specific mechanism of active transport.
  • Unlike the mammalian cells, the bacterial tubes seem to have no "railroad" to guide the transported molecules.
       

The question is :

Can we develop a theoretical model of "active" transfer that can justify what was observed in the orignal article?

We need to know if such a model can be designed starting from physical laws and if this model can explain quantitatively the transfer through the nanotubes. Due to its purely physical nature, our model can also shed some light as to the nanotube formation.

We managed to come up with an idea for such a process, and in this page we propose a new model that can possibly explain the speed of the molecule exchange through the nanotubes.

As a matter of fact, the difference in membrane tension between two bacteria could lead to a pressure difference. That could induce a small cytoplasmic transfer to reach internal pressure equilibrium.

Summary

Click on the circles on the above picture to discover our assisted diffusion model in details

Model description in few words :

We do not know what is the mechanism behind nanotube formation. We can suppose they are made of lipid membrane within a cell-wall like matrix, as suggested by the original electron microscopy experiment. When the membrane of the two cells fuse, there might be a difference of tension between the two phospholipid bilayers. This phenomenon might lead to a movement of lipids from one membrane to the other. The newly arrived phospholipids change the membrane tension of the bacterium. As a consequence, they change the internal Laplace pressure ΔPLap of the bacterium.

where τ is membrane tension, R is a radius of bacterium.

A simple analogy of clothesline can help to understand what is happening. You need to pull more your clothesline to put more clothes on it. When you pull the rope by two ends you create a tension. The bigger the tension, the more weight (pressure) you can put on the rope.

All of this will lead to establishing the pressure difference at the tube extremities and we will get a Poiseuille's flow. Constituents diluted in water will move from one cell to another unidirectionally and faster than by simple diffusion. This is a fast process that we have named the "assisted diffusion".

The assisted diffusion model in 3 bullet points:

  • Characteristic time of the process is about 100 ns
  • The effect strongly depends on the initial phospholipid distribution on the membrane of two connected bacteria
  • The phenomenon predicts the flux of only 0.1 % of the cytoplasme, not enough to explain the GFP experiment of the original paper

We have done a back of the envelope calculation to see whether an order of magnitude is acceptable.

References

  1. Intercellular Nanotubes Mediate Bacterial Communication, Dubey and Ben-Yehuda, Cell, 2011, available here
  2. BioNumbers here