In silico simulation of epithelial cell tubulogenesis

By improving our understanding of epithelial cell tubulogenesis in vitro we should improve our understanding of how these cells organize to form normal tissues such as the ducts and lobules that make up breast tissue. We do not fully understand how these ducts and lobules form. Because it is difficult to directly control and observe epithelial cell morphogenesis in vivo, we study it using in vitro culture systems. They are more easily controlled and observed. One of the most well studied models of tubulogenesis uses Madin-Darby canine kidney (MDCK) cells in culture systems: single cell layered cysts form tubules when exposed to hepatocyte growth factor (HGF). We have developed an in silico analogue that mimics the fundamental cell-level operating principles and system-level phenotypes of in vitro MDCK tubulogenesis. The creation and validation of the analogue required the specification and questioning of currently held assumptions. The analogue can be used to test hypotheses about mechanisms and in silico operating principles that may have in vitro counterparts. By increasing our understanding of the operating principles that govern in vitro epithelial cell growth and organization we are better positioned to understand how best to manipulate these operating principles to achieve specific tissue engineering objectives.