Introduction

The model has two parts: first part of the model simulates the growth and maintenance of cell population under satisfied nutrient condition. The second part of the model takes individual cell motility into consideration and attempted to capture the decision making and orienting processes of each cell. The main difference between two parts is that the first part considers population-level cellular activity while the second part considers cells individually with each cell having a specific coordinate.

Part One: Growth and Maintenance Simulation

Description

Based on the assumption that the pellicle growth is linearly proportional to glucose, acetate and oxygen consumption, a model is constructed to visualise the varying two dimensional profile of nutrient concentration. In particular, this is done with respect to nutrient depletion, periodic addition and diffusion within the culture environment. The model can be used to identify regions suitable for cell growth based on local nutrient concentration profiles. As result, a map of cell density distribution can be obtained.

Simulations of Nutrient Profiles

Oxygen Profile

Glucose Profile

Simulation Conditions

1. Cell growth occurs only when nutrient conditions are satisfied and cell growth is dependent on local oxygen, glucose and acetate concentration;
2. For unit cell, uptake of nutrient for maintenance is constant;
3. Cell population is increasing exponentially;
4. Bacterial cellulose is only produced with the presence of cells and BC production is linearly proportional to cell population;
5. Glucose consumption for bacterial cellulose is linearly proportional to cell population where glucose is directed to both cellulose production and cell growth and maintenance.
6. Nutrients (glucose and acetate) are added periodically on the top of the media.

Interaction with Wetlab

By simulating the nutrient diffusion and depletion processes, the model can be used to compute a nutrient addition schedule and to simulate the impact of different nutrient supply rates.

Part Two: Orientation and Mobility Consideration

Description

Based on the nutrient profiles obtained from simulations of the first part of the model, the second part is designed to account for cell movement along high-nutrient gradients. This second part of the model thus aims to capture chemotaxis, i.e. the ability of cells to sense their surrounding nutrient environment and consequently move towards nutrient-rich regions.

Simulations of Nutrient Profiles

Oxygen Profile

Glucose Profile

Simulation Conditions

Based on the simulation conditions described in part one of the model, the second part of the model is used to capture the effects of cell movement towards nutrient rich regions (chemotaxis). The “decision” for cell movement is based on the cell’s need for nutrient, i.e. acetate or glucose. The cell will first make a decision about its nutrient need according to its local nutrient status: if the local nutrient concentration does not meet its growth requirements, then the cell will move towards the closest region with a richer nutrient concentration. Otherwise, the cell will either stay where it is or move randomly around its current position.

Interaction with Wetlab

Model simulations provide a visual representation of cell movement, which, in turn, allows for a better understanding of cell location and topological density within the system. The model also provides a means to confirm the observation that BC is mainly produced at the surface of the liquid media (where cells have an adequate access to oxygen), which also has an implication on the upregulating effect of oxygen on BC production.

Appendix: Code

The code for this model can be found here: Nutrient_Diffusion_Simulations_Imperial_iGEM_2014.m