A robust in silico analogue of MDCK cystogenesis mimics growth in multiple culture conditions

Madin-Darby canine kidney (MDCK) cells undergoing cystogenesis in vitro is a scientifically useful model of epithelial morphogenesis. The cysts formed in collagen and Matrigel are qualitatively similar, consisting of a single layer of epithelial cells surrounding a hollow lumen. However, differences in key quantitative measures of cyst growth, including cell number and cyst and lumen size, indicate that some cell behaviors are different within the two culture systems. We recently described an agent-oriented analogue of MDCK cystogenesis in Matrigel. It utilized a cellular Potts model and achieved qualitative and quantitative validation targets using empirical parameter tuning. Within this report we highlight steps taken to convert the cellular Potts model framework to one based upon an agent-oriented approach. If measures of cell death are ignored, the only parameters that required adjustment to allow the analogue of cystogenesis in Matrigel to mimic MDCK cystogenesis in collagen were those controlling cell division and polarization. These data indicate that in addition to delayed cell polarization, cell division in collagen is likely slower than in Matrigel. The reported results support the hypothesis that MDCK cells use the same basic operating principles to create cysts when cultured in Matrigel or collagen.