Stem cell niches are tissue sites which provide a microenvironment that enables stable self-renewal of somatic stem cells. In the intestine the stem cell niche has been thought for a long time to be located at the bottom of the crypts of Lieberkühn, but only recently their functional constituents have been identified. In fact, Paneth cells have been demonstrated to contribute to niche function by providing essential signals for both maintenance and renewal of the stem cells. During crypt fission the entire niche structure replicates. A mechanistic understanding of this process is not available, so far.

We have developed a 3D individual cell-based computational of intestinal tissue which allows simulating changing tissue morphology as observed during intestinal organoid formation in vitro and during crypt fission in vivo. To account for such shape changes we introduced a flexible basal membrane. This allows us to assign an elastic and a bending modulus to the tissue surface. Accordingly, the tissue surface is continuously re-organized by cells attached to it, depending on the cells’ differentiation status. Thus, the morphology of the epithelium is self-organized.

Here, we present simulation studies where we have assumed that local tissue curvature controls Paneth cell specification. We demonstrate that according to this assumption the stability of the niches depends on the balance between the biomechanical properties of the tissue and the cells’ proliferation activity. Decreasing bending rigidity of the tissue and/or increasing the cells’ proliferation activity, niches become destabilized. As a consequence they multiply resulting in tissue growth.

Thus, according to our model, tissue biomechanics are expected to strongly influence the formation and perpetuation of intestinal stem cell niches.