Revision as of 21:33, 30 October 2017

Behavior of CATE inside Tumor

We developed a model to gauge the behavior of our sensing circuit in the real life conditions of solid tumor colonization. Since it was not practically feasible to conduct experiments of bacterial colonization inside tumors, we used results from reference to simulate colonization in a thin spherical layer inside a solid tumor.

The COMSOL model helped us to extend our MATLAB model in the following ways:

Diffusion physics of AHL was included to extend the ODEs into PDEs

Our MATLAB model does not take into account diffusion of AHL, since in the viable lab experiments (in test-tubes), the only sink for AHL is its degradation. However, in a tumor as explained in reasoning, diffusion has much more significant contribution than degradation. Thus our model helped us gauge and verify the behavior of our tumor-sensing circuit in more real-life conditions pertaining to the intended application context. Using the results obtained from our simulations, we could check the behavior of the AND gate functioning in different conditions of d_cell and lactate.
Diffusion physics of Azurin was included to simulate the effect of lysis

To simulate the effect of lysis, our COMSOL model stops the production of Azurin and starts its diffusion when temperature reaches 42°C. This simulates the effect of increase in temperature with FUS to cause cell lysis. Using data obtained from such a simulation, we could also find the temporal-maximum concentrations of Azurin at each point in the tumor, effectively helping us to estimate the killing area.

Using our model, we also tried a few other colonization patterns to show our system works as expected inside a tumor while stays dormant in healthy tissue. We simulated the following patterns:

Homogeneous distribution in a Single spherical-shell-shaped layer in Tumor
Heterogeneous distribution in a Single spherical-shell-shaped layer in Tumor
Heterogeneous distribution in Double spherical-shell-shaped layer in Tumor
Homogeneous distribution in Healthy tissue

Model Overview

Parameters
Equations
- Growth phase
- Sensing (AHL and LuxI)
- Azurin
Assumptions

Results

Beautiful GIFs coming soon .... MUST REALLY SOON

CASE: Tumour colonization - High d_cell AND High Lactate
CASE: Healthy tissue colonization: High d_cell AND Low Lactate

Figure 1. Normalized concentration of AHL and Azurin, Cell density (as a ratio of its steady state value), P_luxlldR and Temperature (as a ratio of its steady state value 42°C).
CASE: Tumour not colonized: Low d_cell AND High Lactate
CASE: Healthy tissue not colonized: Low d_cell AND Low Lactate

Bacterial colonization patterns