Spatial Constraints On In-Vitro Cancer Cell Line Growth

Population density puts a constraint on cell growth through the mechanism of contact inhibition. Dysregulation of this process is one of the hallmarks of cancer. Contact inhibition is correlated with expression of pathways associated with E-cadherin signaling such as Hippo and Wnt, or inhibition of mTOR signaling. We observe heterogeneous expression of these pathways across and within nine metastatic gastric cancer cell lines via single cell RNA sequencing data. Our working hypothesis is that high or low population densities will benefit certain cells over others, selecting for subclonal populations in an evolutionary process known as density dependent selection. Here, we present a method which integrates cell culturing experiments with single cell sequencing data to investigate the effects spatial constraints have on subclonal growth of cancer cells in-vitro. Our results evaluate the usefulness of population density as an informer of subclonal growth dynamics in a data driven, mechanistic model.