Difference between revisions of "Team:KU Leuven/Modeling/Top"

The video above shows how the proposed method for pattern formation works. Two cell types A and B are interacting. Type A cells produce a repellent called leucine which causes the cells of type B to move away. At the same time type A cells also produce AHL, which is required by the cells of type B to move. Initially, colonies of the two cell types are placed at the center of the dish. As molecule production within the type A cells kicks in, the repellent and AHL concentrations start to increase. This triggers the type B cells to move away from the center. Movement will continue until the concentration of AHL is insufficient for the type B cells to move further.
The Keller-Segel type model we used is given by the following equation system: $$\frac{\partial A}{\partial t} = D_a \bigtriangledown^2 A + \gamma A(1 - \frac{A}{k_{p}}),$$ $$\frac{\partial B}{\partial t} = D_b \bigtriangledown^2 B + \bigtriangledown (P(B,H,R) \bigtriangledown R)+ \gamma B(1 - \frac{B}{k_{p}}), $$ $$ \frac{\partial R}{\partial t} = D_r \bigtriangledown^2 R + k_r A - k_{lossH} R $$ $$\frac{\partial H}{\partial t} = D_h \bigtriangledown^2 H + k_h A - k_{lossR} H . $$ With:
$$ P(B,H,R) = \frac{-B K_{c} H}{R}. $$ The model has been derived while looking at ^[1] and ^[2] . The terms that appear can be grouped into four categories. Every equation has a diffusion term given by $D_x \bigtriangledown^2 X$, diffusion smoothes peaks by spreading them out in space. The two equations related to cell densities contain logistic growth terms of the form $\gamma X(1-\frac{X}{k_x})$, which model the cell growth during simulation time. Finally the second equation describing the moving cells comes with a variable coefficient Poisson term $\bigtriangledown (P \bigtriangledown X)$ which describes the cell movement. Last but not least: the two bottom equations. They model concentrations, contain linear production and degradation terms, which look like $kX$.
To generate the video file above the system above has been discretized using a finite volume approach in conjunction, with an explicit Euler scheme:

The image above shows the dependency of data in time and space. The computational molecule used in this case uses only data of the previous time level $t_n$ to compute data at the next time level $t_{n+1}$. A scheme with a space time dependency like the one shown above is called an explicit scheme. Periodic boundary conditions have been implemented, which means that cells leaving at the top of the boundary appear at the bottom, cells leaving at the left boundary reappear at the right and so on. Finally simulation has been done using the parameters given in the table below:

Parameter	Value	Unit	Source	Comment
$D_a$	$0.072 \cdot 10^{-3}$	$cm^2/h$	following [1]
$D_b$	$2.376 \cdot 10^{-3}$	$cm^2/h$	following [1]
$D_r$	$26.46 \cdot 10^{-3}$	$cm^2/h$	as found in [6]	$298.2 K$
$D_h$	$50 \cdot 10^{-3}$	$cm^2/h$	from [3]
$K_{c}$	$8.5 \cdot 10^{-3}$	$cm^2 \cdot cl/h$	estimated
$\gamma$	$10^{-5}$	$h^{-1}$	from [1]
$k_p$	$1.0 \cdot 10^2$	$cl^{-1}$	from [1]
$k_h$	$17.9 \cdot 10^{-4}$	$fmol/h$	computed from [4] and [8]
$k_r$	$5.4199\cdot 10^{-4}$	$fmol/h$	computed from [7] and [8]
$k_{lossH}$	$1/48$	$h^{-1}$	from [5]	$ ph = 7$
$k_{lossR}$	$1/80$	$h^{-1}$	estimated

Initial condition 1 Initial condition 2 Initial condition 3 Initial condition 4 Random initial data periodic boundary zeroFlux boundary https://static.igem.org/mediawiki/2015/0/0c/KU_Leuven_ZeroFluxBoundary.ogg

Using the equation system as described above, the model may also be simulated in two dimensions. Once more a finite volume approach has been taken in connection with an explicit Euler scheme. All parameters have been kept constant with the one exception of the chemotactic sensitivity $K_c$. Which has been increased to $Kc = 1.5 * 10^{-1}$$cm^2/h$, which leads to earlier pattern formation. Above simulation videos with several initial conditions can be observed.

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