In multicellular systems, cells of different types interact in various ways, both mechanically and chemically, to regulate complex processes. There is a large computational gap between detailed models of sub-cellular, molecular processes in single cells, and models of multicellular systems comprising of large numbers of interacting cells such as bacterial colonies, tissue and tumors. In the lab we seek to bridge this gap. We also develop new simulation methodology for modeling specific biological systems together with collaborators.
Scaling mechanisms of cartilage sheets
During embryo development cartilaginous structures assemble that later densify into bone and form the basis for the embryo’s skeleton. Understanding the cellular dynamics responsible for the correct shaping and growth of the cartilage is hence of high importance for modeling the full embryogenesis.
In this collaboration with the Adameyko lab at the Karolinska Institute we study the key question of how mechanical interactions and individual behavior at the cellular level enable the accurate shaping of the cartilage sheet. In order to analyse the influence of different mechanisms in-silico, we built a computational model of the cartilage sheet, combining the center-based model (CBM) as a mathematical framework for the cellular mechanics with rules governing the cellular behavior based on biological observations. We validate the model against in-vivo data, obtained from cell-lineage tracing performed by the Adameyko Lab .
- Kaucka, M., Zikmund, T., Tesarova, M., Gyllborg, D., Hellander, A., Jaros, J., … & Dyachuk, V. (2017). Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage. eLife, 6, e25902.2
- Marketa Kaucka, Evgeny Ivashkin, Daniel Gyllborg, Tomas Zikmund, Marketa Tesarova, Jozef Kaiser, Meng Xie, Julian Petersen, Vassilis Pachnis, Silvia K Nicolis , Tian Yu, Paul Sharpe, Ernest Arenas, Hjalmar Brismar, Hans Blom, Hans Clevers , Ueli Suter, Andrei S Chagin, Kaj Fried, Andreas Hellander and Igor Adameyko, (2016) Analysis of neural crest-derived clones reavals novel aspects of facial development, Science Advances 2(8).