TissueOpt

The purpose of this project was to develop the Tissue Simulation Toolkit 2.0 (TST 2.0), a software library that is used by the computational biology community to simulate the single cell and collective behavior of animal cells, extracellular materials and signals during embryonic development, blood vessel formation, in cancer and in cell cultures.

The software implements the widely used cellular Potts model (CPM), a lattice-based simulation technique to simulate cell behavior and tissue development. The TST specializes in hybrid cellular Potts models, which are CPMs coupled with other techniques, such as partial-differential equations and molecular dynamics (MD) methods to represent the extracellular and intracellular matrix environment.

Concretely, this project focused on the optimization of a hybrid MD-CPM model that is used to study mechanical and chemical interactions between the cell and the extracellular matrix (ECM). The model describes one or more contractile biological cells, embedded inside a fibrous ECM. The model simulates how the cell locally deforms the ECM and, vice versa, how forces from the ECM affect the adhesions of the cell and the ECM.

At the start of the project, we were limited to simulating two or a few static, contractile cells. Thanks to the project, the TST-MD model can now also model also cell migration on top of fibrous matrices, involving dynamic attachments and detachment of the cells to the ECM. Also the software has become sufficiently efficient so as to allow simulations of several tens of cells embedded in an extracellular matrix.

The user community consists of our own group and a national and international groups, consisting of biologists, theoretical biologists and biophysicists. The impact of the software is best illustrated by a list of research papers that have used Tissue Simulation Toolkit, maintained at https://mathbioleiden.nl/software.html.