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In these cultures intestinal cells expressing the stem cell marker Lgr5 form crypt- like structures similar to those found in vivo. The mechanisms that underlie the formation of these spatially-organised structures are currently a matter of debate. We here present a 3D biophysical model of de novo crypt formation in vitro. The model builds on an individual cell-based model of crypt dynamics recently published by us [2]. We extended this model by introducing a flexible basal membrane. This membrane can be reorganised by cells showing active matrix metabolism. In this model, shape changes of the basal membrane result from a feedback loop between its curvature and the Wnt-activity of adherent cells. Thereby, increased Wnt-activity increases the adhesion strength of the cells and thus, forces local shape changes of the basal membrane. We demonstrate the formation of crypt-like structures within this model depending on the elasticity and stiffness of the basal membrane and on the adhesion properties and matrix metabolisms of the different cell types. We propose that the mechanisms investigated here for morphogenesis in vitro are also at acting during tumor invasion.
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| © 2011 Physics of Cancer | Soft Matter Physics Division, University of Leipzig. Imprint & Disclaimer | |||||||||||||||||||||||||
