Understanding the link between intracellular information and the large scale dynamics of tumors and tissues, and identifying the major quantities on smaller scales that determine the system behavior on larger scales is a major challenge.
This talk aims to make some steps into this direction starting with single cell models which are primarily biophysical and stepwise including properties inherent to biological cells such as differentiation and regulation.
Firstly a model to growing monolayers and tumor spheroids is proposed in which each cell is represented individually and parameterized by experimentally measurable cell-biophysical and cell-kinetic parameters. Hence our modeling strategy in principle allows to study which mechanisms on the microscopic level of individual cells determine the macroscopic properties of tumor growth. In a next step we show how this model may be used to derive simpler models that still contain the major feature of the dynamics. As illustrated our models give a good quantitative agreement with experimental data and provides testable predictions without the need to take into account differentiation. For the transition from a blastula to a gastrula this is no longer the case: here a normal embryonic development would derail if no differentiation would occur. However, modeling blastulation and gastrulation implies that the cell differentiation that leads to the invagination is known apriori. In a simple model to cell migration and aggregation we illustrate how cell behavior may be guessed in case the cell behavior, or a cell differentiation is not known apriori. The latter includes the coupling between intracellular regulation, cellular phenotype and evolution.
References
Drasdo, D. and Forgacs, G., 2000, Modeling generic and genetic interactions in Cleavage, Blastulation and Gastrulation. Dev. Dyn. 219 (2) 182-191.
Drasdo, D., 2003, On selected individual-based approaches to the dynamics in multicellular systems. In Polymer and Cell Dynamics: Multiscale Modelling and Numerical Simulations (Eds. W. Alt, M. Chaplain, M. Griebel, J. Lenz), Birkhäuser, Basel.
Galle, J., Loeffler, L. and Drasdo, D., 2003, An individual-cell based model of the growth regulation of the epithelial cell populations in vitro. German Conference on Bioinformatics.
Drasdo, D. and Hoehme, S., 2003, Individual-based approaches to birth and death in avascular tumors.
Mathematical and Computer Modelling 37, 1163-1175.Galle, J., Loeffler, L., and Drasdo, D., Modelling the effect of deregulated proliferation and apoptosis on the growth dynamics of epithelial cell populations in vitro. Biophys. J. (in press).
