Team:Paris/DryLab

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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

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.


Delay System.jpg

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


Indeed, the over expression of TolRII takes an important part in the creation of vesicles, disturbing the Tol-Pal system which act as a physical anchor for the outer membrane to the cell-wall:

  • We demonstrate (Details) that the formation of blebbing is due to this anchor system and to the osmotic pressure increase caused by the peptidoglycan turnover.
Vesicle wiki.jpg

figure: Blebbing simulation obtain for random Tol/Pal distribution.


  • We show that an accumulation of protein in the aera of negative curvature is explainable by simple diffusion mechanism.


  • We show that this two phenomenon linked together can explains the whole maturation of a blebbing in a vesicle.


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.