Colonic Crypts with VCell and SBML/Spatial

The physiological working of colonic crypts is dependent on the specific dynamic spatial organization of various cell types. The colonic crypt is characterized by a high rate cell renewal, and the proper functioning of the structure is ensured by a complex cell differentiation process occurring over different tissue layers. Proper simulations of colonic crypt dynamic requires the modeling of both temporal and spatial dimensions. To this end, we performed a modeling exercise using the recently developed SBML3 Spatial Processes package, in conjunction with the NRCAM UConn VCell software in order to model colonic crypts. The SBML3 Spatial Processes package allows for the representation of geo- metric and topological features on top of the normal dynamic modeling SBML capabilities. We verified that with the proper use of the different SBML fea- tures it is possible to define an extensive model of colonic crypts composed of the main cellular types (from stem cells to fully differentiated cells), alongside their dynamics. The different cell types have been arranged to form a hollow prism placed in a 3-dimensional cartesian reference frame mimicking the structure of the colonic crypt. Despite the elementary and approximated model structure (and therefore less relevant from the biological viewpoint, compared to several already developed and published models), we have already seen that our model is capable of capturing important cell crypt structure and behavior. As such, this provides one of the first validations of the SBML3 Spatial Processes package, applied to a non-trivial system.