Difference between revisions of "Team:ETH Zurich/Modeling/Reaction-diffusion"
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Revision as of 15:37, 20 August 2015
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Reaction-diffusion Models
Introduction
While single-cell models are useful for correctly implementing and debugging chemical reaction models, they are not sufficient to fully understand the real-life functionality of our system. Since an essential part of our system is increasing the perceived concentrations of lactate and AHL through co-localization, it is necessary to model the concentrations the chemical species though a reaction-diffusion system.
3D model
Four cases
To test whether our system acts as an AND gate on our two inputs (higher lactate production and co-localization signals), we combinatorially tested all possible combinations high vs. low lactate production and E. coli co-localization vs. dispersion.
Diffusion and transport of chemical species
Under alkaline conditions, E. coli actively import lactate via a proton-motive symporter. Thus, a cross-membrane transport reaction had to be implemented. Since this is not possible directly in COMSOL, we had to model lactate in two states. Suppose our reference is the subspace of the interiors of the E. coli. We then defined the two states \(Lac_\text{int}\) and \(Lac_\text{ext}\), denoting intracellular and extracellular lactate, respectively. \(Lac_\text{ext}\) is produced by the target cell and can diffuse freely though the medium and all membranes. \(Lac_\text{int}\) is in equilibrium with \(Lac_\text{ext}\) with rate constants set to maintain a 20-fold difference of lactate concentration between interior and exterior. $$ Lac_\text{ext} \mathop{\mathop{\xrightarrow{\hspace{4em}}}^{\xleftarrow{\hspace{4em}}}}_{k_\text{int}}^{k_{\mathrm{ext}}} Lac_\text{int} \qquad \frac{k_\text{int}}{k_\text{ext}}\approx 20 $$ In addition, only the \(Lac_\text{int}\) state can react with the other chemical species in the E. coli.
AHL is able to freely diffusion in the medium and across membranes. All other chemical species are only able to diffuse intracellularly.
Assumptions
- Target mammalian cell located in the center of the well
- Constant rate of lactate production
- E. coli bound to target cell abstracted into homogeneous layer around target cell
- Two different forms of unbound E. coli
- Discrete: single cell of E. coli suspended in the medium
- Bulk: reactions of the rest of the E. coli simulated in same space as medium
- Lactate represented as two states: inside and outside E. coli, denoted \(Lac_\text{int}\) and \(Lac_\text{ext}\), respectively
- \(Lac_\text{int}\) can diffuse freely through medium and membranes, \(Lac_\text{ext}\) cannot
- Use to simulate different import and export rates of lactate into E. coli
- Bulk E. coli grow logistically
