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 brodland collage

Computational Modeling

The goal of this work is to use computational models to understand the forces that drive cell and tissue motions in contexts such as embryogenesis, regenerative medicine and cancer metastases.

Cell-level Models

Cell-level finite element (FE) models we developed [1-7] ultimately lead to an integrated understanding of the forces that drive a wide range of cell rearrangements (Fig. 1) and revealed why sorting and other processes are different in 2D compared to 3D (Movie 1).

Figure 1

Fig. 1. The new theory we developed, called the Differential Interfacial Tension Hypothesis (DITH), is able to explain all of the morphological transitions shown in this figure.


Movie 1. Simulations of sorting in 3D revealed specific reasons that it is different than in 2D.

 

Tissue-level and Multi-scale Models

In these models [8-9], single finite elements represent groups of cells, and doing so allows whole embryos to be represented. The mechanical properties of these elements are calculated using constitutive equations [10] derived from cell-level models [1-7]. This approach has enabled us to understand how genetic and mechanical aberrations in specific tissues give rise to malformation defects (Fig. 2).

Figure 2

Fig. 2. Multi-scale computational models were used to investigate the mechanics of neurulation and to determine which genetic and mechanical irregularities were sufficient to produce a malformation defect.

References

1. Chen, H.H., and Brodland, G.W., 2000, "Cell-level Finite Element Studies of Viscous Cells in Planar Aggregates", ASME Journal of Biomechanical Engineering, Vol. 122, pp. 394-401. pdf

2. Brodland, G.W., and Veldhuis, J.H., 2002, "Computer Simulations of Mitosis and Interdependencies Between Mitosis, Cell Shape and Epithelium Reshaping," Journal of Biomechanics, Vol. 35, pp. 673-681. URL.

3. Brodland, G.W., and Veldhuis, J.H., 2003, "A Computer Model for Cell Reshaping in Epithelia due to In-plane Deformation and Annealing," Computer Methods in Biomechanics and Biomedical Engineering, Vol. 6, pp. 89-98. doi: 10.1080/1025584031000078934.

4. Brodland, G.W., 2004, "Computer Modeling of Cell Sorting, Tissue Engulfment and Related Phenomena: A Review," ASME Applied Mechanics Reviews, Vol. 57, pp. 1-30. doi: 10.1115/1.1583758.

5. Brodland, G.W., 2006, "Do lamellipodia have the mechanical capacity to drive convergent extension?" International Journal of Developmental Biology, Vol. 50, pp. 151-155. doi: 10.1387/ijdb.052040gb.

6. Brodland, G.W., Viens, D. and Veldhuis, J.H., 2007, "A New Cell-based FE Model for the Mechanics of Embryonic Epithelia," Computer Methods in Biomechanics and Biomedical Engineering, Vol 10 (2), pp. 121-128. doi: 10.1080/10255840601124704.

7. Viens, D., and Brodland, G.W., 2007, "A Three-dimensional Finite Element Model for the Mechanics of Cell-Cell Interactions," ASME Journal of Biomechanical Engineering, Vol. 129, pp. 651-657. doi: 10.1115/1.2768375.

8. Chen, X. and Brodland G.W., 2008, "Multi-scale Finite Element Modeling Allows the Mechanics of Amphibian Neurulation to be Elucidated," Physical Biology, Vol. 5 (1), pp. 1-15. doi: 10.1088/1478-3975/5/1/015003.

9. Brodland, G.W., Chen, X., Lee, P. and Marsden, M., 2010, "From genes to neural tube defects (NTDs): Insights from multiscale computational modeling," HFSP Journal, Vol. 4, pp. 142-152. doi: 10.2976/1.3338713.

10. Brodland, G.W., Chen, D.I.-L., and Veldhuis, J.H., 2006, "A Cell-based Constitutive Model for Embryonic Epithelia and Other Planar Aggregates of Biological Cells," International Journal of Plasticity, Vol. 22, pp. 965-995. 10.1016/j.ijplas.2005.05.002.