Use Cases for Multi-Cell Modeling using the CBO

Here we define a set of use cases for multi-cell modeling in general and the CBO in particular.

The use cases are designed to fully test and to define the scope of multi-cell modeling that can be specified using the CBO. The use cases are organized from the very simple to increasing complex cases. In many cases the more complex use cases are dependent on the proper description (and implementation) of the simpler uses cases.

Basic Use Cases

Cell & Model Basic Definition

This most basic of use case is simply to describe a system with systemic extents and parameters (temperature, pressure, etc.), dimensionality (2, 3, … dimensions), cells (with proper naming and linkages to external ontologies such as FMA) and an initial configuration of the cells and medium.

Cell Motility

Cell motility is the active motion of a cell. For this use case we are interested in undirected motility. (Directed motility, e.g, chemotaxis and haptotaxis, will be addressed in a later use case.) Instead of describing the detailed molecular mechanisms underlying motility, for example the dynamics of actin filaments, microtubules and the intermediate filaments, we instead focus on describing the microscopically observable changes.

There are at least two ways to define this type of motility. It could be defined in terms of a wave amplitude and frequency of fluctuations of the cell membrane or, more simply, as the mean free velocity or mean squared displacement of the cell. Measured random motilities range from zero to more than 50 υm/min.

Cell Sorting (Cell-Cell Interaction)

Cell Growth

The growth of a cell will be described as a basic growth rate equation, expressed in MathML. No specific direction of growth is specified and the modeled cell grows in a random direction.

In real-world models the simple growth rate equation may be replaced by more complex relationships including variables derived from other models.

Cell Division

Cell division will be described as a basic volumetric threshold function. Starting with the Cell Growth use case we will add that when the cellular volume exceeds a given threshold the cell divides into two identical daughter cells. Two cases are presented, in the first case the cell cleavage plane is randomly oriented, in the second, the cleavage plane is defined relative to the coordinate system.

Cell Division Case I: Random orientation of cleavage plane

Cell Division Case II: Defined orientation of cleavage plane

Avascular Tumor

Vasculogenesis

Vascular Tumor

Epithelium

Chemotaxis

Haptotaxis

Cf. figure 2 in A stochastic model for adhesion-mediated cell random motility and haptotaxis
Cell Motility as Persistent Random Motion: Theories from Experimentsk

More Complex Use Cases

Somitogenesis in Chicken

Gastrulation in Zebrafish

Gastric Crypt

Liver Lobule

Lung Airways

Macrophage chasing Bacterium

Chasing

Delta / Notch Lateral Inhibition

Plant Roots

Dermis

Macrophage Invasion / Extravasation ...

Delta/Notch Lateral Inhibition