A multiscale model of intestinal crypts dynamics

Intestinal crypts are multicellular structures the properties of which have been partially characterized, both in the “normal” and in the “transformed” development. Only in the last years there has been an increasing interest in using mathematical and computational models to achieve new insights from a “systems point-of-view”. However, the over- all picture lacks of a general model covering all the key distinct processes and phenomena involved in the activity of the crypt. Here we propose a new multiscale model of crypt dynamics combining Gene Regulatory Networks at the intra-cellular level with a morphological model com- prising spatial patterning, cell migration and crypt homeostasis at the inter-cellular level. The intra-cellular model is a Noisy Random Boolean Network ruling cell growth, division rate and lineage commitment in terms of emergent properties. The inter-cellular spatial dynamics is an extension of the Cellular Potts Model, a statistical mechanics model in which cells are represented as lattice sites in a 2D cellular automaton successfully used to model homeostasis in the crypts.