MDCK Cystogenesis Driven by Cell Stabilization Within Computational Analogues

Epithelial cells perform essential functions throughout the body, acting as both barrier and transporter and allowing an organism to survive and thrive in varied environments. Although the details of many processes that occur within individual cells are well understood, we still lack a thorough understanding of how cells coordinate their behaviors to create complex tissues. In order to achieve deeper insight, we created a list of targeted attributes and plausible rules for the growth of multicellular cysts formed by Madin-Darby canine kidney (MDCK) cells grown in vitro. We then designed in silico analogues of MDCK cystogenesis using object-oriented programming. In silico components (such as the cells and lumens) and their behaviors directly mapped to in vitro components and mechanisms. We conducted in vitro experiments to generate data that would validate or falsify the in silico analogues and then iteratively refined the analogues to mimic that data. Cells in vitro begin to stabilize at around the fifth day even as cysts continue to expand. The in silico system mirrored that behavior and others, achieving new insights. For example, luminal cell death is not strictly required for cystogenesis, and cell division orientation is very important for normal cyst growth.

Project Contact: Jesse A. Engelberg

Collaborators: Anirban Datta, Keith E. Mostov

In Silico MDCK Analogue Supplementary Material:

The premise of the agent paradigm, its related theory and methodologies together with advances in multilevel modeling of complex systems of interactions opened new frontiers for advancing the physical, natural, social, military, and information sciences and engineering...