The multiscale in silico liver

similarities to glandular carcinoma. On the other hand, dysregulation of the in silico principle governing proliferation had muted effects on growth morphologies. Comparatively, the 2 alterations and their misbalance gave rise to distinct morphologies that mark intermediate stages of a simulated progression toward malignancy. In cases where unchecked growth was observed, we identified structural patterns that are similar to observations of epithelial cancer in vivo, such as solid nests and regions of matrix surrounded by cells but in a disorganized pattern. Conclusions: Considered together, our simulations demonstrate how computational models of this type can be interrogated and manipulated to test hypotheses and attain mechanistic insight that encompass seemingly varied aspects of morphogenesis in vitro. The results reaffirm the hypothesis that the composition and arrangement of the extracellular environment have a strong influence on overall morphogenic outcome. They also show that even a slight alteration or dysregulation of a normal in silico operating principle can cause substantial changes in growth characteristics, and suggest that the normal morphogenesis of epithelia tolerates very little deviation from strict adherence to principles of operation. Experimenting with simulation models of this type is expected to provide a potentially fruitful new strategy to gain deeper insight into the operational causes of oncogenesis and identify new targets of cell-based therapies for cancers of epithelial origin.