Research > Simulation Modeling of Epithelial Morphogenesis and Malignancy

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 HJ Kim

Collaborators: Wei Yu, Keith E. Mostov, Jayanta Debnath

Selected Publications and Supporting Data

1. Simulation Modeling of Cyst Formation by Alveolar Type II Cell Culture (in preparation)
• Video 1: Simulated AT II culture (random cell migration) with 2.5 x 10⁴ cells/cm²

• Video 2: Simulated AT II culture (random cell migration) with 10 x 10⁴ cells/cm²

• Video 3: Simulated AT II culture (random cell migration) with 25 x 10⁴ cells/cm²

• Video 4: Simulated AT II culture (chemotaxis) with 2.5 x 10⁴ cells/cm²

• Video 5: Simulated AT II culture (chemotaxis) with 10 x 10⁴ cells/cm²

• Video 6: Simulated AT II culture (chemotaxis) with 25 x 10⁴ cells/cm²

• Video 7: Simulated AT II culture (cell density-based migration) with 2.5 x 10⁴ cells/cm²

• Video 8: Simulated AT II culture (cell density-based migration) with 10 x 10⁴ cells/cm²

• Video 9: Simulated AT II culture (cell density-based migration) with 25 x 10⁴ cells/cm²

2. Simulation Modeling of Epithelial Morphogenesis and Malignancy In Vitro (in preparation)
3. 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