Agent-based Simulation Modeling of Epithelial Morphogenesis and Malignancy

Epithelial morphogenesis is a fundamental process of development whereby unorganized single cells give rise to coherent forms of tissues, organs and ultimately a whole organism. During morphogenesis, individual cells collectively exhibit self-organizing behaviors as they undergo cycles of growth, migration and differentiation driven by their genetic program and environmental conditions. An essential, yet poorly understood, aspect of morphogenesis concerns with how the various morphogenic processes of single cells are regulated and coordinated to establish recognizable patterns of multicellularity.

Currently we are developing a foundational class of computational models to dissect generative principles of cell action that govern epithelial morphogenesis and malignancy in vitro. The developed models are multi-agent systems composed of autonomous in silico cells whose actions are governed by a set of axioms. Our current study focuses on simulation of two types of epithelial cells: (1) Madine-Darby canine kidney (MDCK) cell growth under varying culture conditions, and (2) primary human alveolar type II (AT II) cell alveolization under 3D culture condition.

Project Contact: Sean H. J. Kim

Collaborators: Wei Yu, Keith E. Mostov, Michael A. Matthay, Jayanta Debnath

Supplementary Material

  1. In silico epithelial analogue (ISEA)
  2. Source codes and supporting files:

  3. A Computational Approach to Understand In Vitro Alveolar Morphogenesis
  4. Source codes and supporting files:

  5. Simulation Modeling of AT II Cell Wound Healing (in preparation)

    Note: simulation space is hexagonal, so when one observes a hexagonal cyst it corresponds to a cross-section through a roundish AT II cyst in vitro.  In case of simulated monolayer repair, the in silico visualization corresponds to the xy-planar view in vitro

  6. Kim SHJ, Park S, Yu W, Mostov KE, Matthay MA, Hunt CA. 2007. Systems Modeling of Alveolar Morphogenesis In Vitro.  ISCA 20th International Conference on Computer and Applications in Industry and Engineering (CAINE 2007), San Francisco, California, USA, November 7-9, 2007    CAINE'07 ATII Simulation

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...