Team:Paris/DryLab

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Contents 1 DryLab 2 Main 2.1 Questions 2.2 Results

DryLab

Main - Introduction - Vesicle model - Delay model - Fec simulation Main

Main

Questions

Our Message in a Bubble project aims at developing a communication system between bacterias. Among the various problems raised during the design phase, we investigated 3 of them with modeling and simulation:

• What is the link between Tol/Pal expression and vesicule formation? Or, more precisely, can we explain vesicule formation solely by the diffusion of the doubly anchored Tol/Pal complex in the membrane ? Understanding this connection is instrumental, since our project relies on the hypothesis that an increased in vesicule formation can be obtained simply by destabilization of the Tol/Pal complexes.

• How to improve the quality of the signal sent? Or more precisely, how can we get a good synchronisation between the maximal production rate of vesicules and the maximal concentration of proteins to encapsulate ?

• How to optimize the quality of the reception? Or more precisely, how can we get a robust response despite a potentially very low number of signals (ie, vesicles) recieved ?

Results

• Understanding the link between Tol/Pal expression and vesicule formation

Overall, we showed that the formation of vesicles can be simply explained by the diffusion of Tol/Pal protein complexes. This very surprising result comes from 3 specific phenomena:

• The initial formation of small blebs can be explained by differences of osmotic pressures between intra- and extra-cellular environments, together with a non-perfectly uniform distribution of Tol/Pal complexes acting like press studs. (Details)
• At the basis of nascent blebs, where the outer membrane is non-flat, the simple diffusion (ie Brownian motion) of doubly-anchored Tol/Pal molecules leads to their accumulation.
• Rings of accumulated Tol/Pal at the basis of nascent blebs tend to constrict: vesiculation happens. This again simply results from plain Brownian motion on non-flat surfaces.

figure: Initial formation of small blebs resulting from intra- and extra-cellular osmotic pressures differences combined with non-perfectly uniform distribution of Tol/Pal complexes acting like press studs between the internal membrane and the outer membrane.

• Improving the quality of the signal sent

To create a delay between the maximum concentration of proteins and of the maximum creation of vesicules by time units, we used a transcriptional cascade inside the genetic network thus synchronising protein and vesicule creations.

Plot showing that vesiculation happens only once the protein encapsulated has reached its maximal concentration.

• Optimizing the quality of message reception

Concerning reception, stochastic simulations revealed two possible problems reducing the robustness of our reception system :

• when the amount of messengers received is too weak, the activation does not always occur
• even when it occurs, the activation time can vary.

After trying various solutions in our modeling study, we proposed to introduce an over expression of FecR protein to solve this problem ; simulations showed a good and robust activation in this case.