Linking Changes in Epithelial Morphogenesis to Cancer Mutations Using Computational Modeling
Figure 3
3D MCF10A-tuned morphocharts of epithelial mutants.
A 3D parameter space of the MCF10A-tuned model defining cell sensitivity to proliferating, apoptotic and ECM-density cues. A dark-red region represents a subspace of MCF10A-comparable acini. The green region defines a subspace of model parameters producing non-stabilized morphologies representing the potentially invasive mutations of the MCF10A baseline: (i) non-polarized structures showing no cell growth; (ii) non-stabilized structures with growing cells observed only on the outer rim; (iii) disorganized structures with multiple cells growing throughout the cell cluster, and with sporadic apoptotic events; (iv) non-stabilized structures with multiple proliferating and apoptotic events; (v) non-polarized but hollow structures with an outer rim containing multiple growing cells. Four genetic mutants of the MCF10A parental cell line shown in (I–IV) can be mapped onto the IBCell morphochart in a qualitative way by comparing morphologies of simulated (i–v) and experimental (I–IV) cell clusters.