IBCell Morphocharts: A Computational Model for Linking Cell Molecular Activity with Emerging Tissue Morphology

Katarzyna A. Rejniak

Abstract: Despite the fact that many genes and signaling pathways responsible for early carcinoma lesions have been identified, it is not yet fully understood how these molecular defects produce emergent abnormal morphologies. Nonetheless, morphological changes in three-dimensional multicellular cultures provide the first insight into invasive potential of cells and phenotypic/genotypic changes when compared with normal nontumorigenic morphologies. Thus, a quantitative tool for matching the molecular and morphological scales can be useful for designing testable experimental hypotheses. The computational model presented here can capture both the spatial and the temporal dynamics of developing multicellular structures and produces multidimensional charts (morphocharts) of various acinar and mutant morphologies arising from simultaneously varied model parameters. These morphocharts allow us to map experimental morphologies onto the model parameter space to identify deregulated molecular processes that can be subjected to further experimental validation. This approach provides mechanistic information on intermediate scales between molecular pathways and multicellular organization.