Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Hybrid cell-based modeling of mechanical cell-matrix feedback during collective cell behavior
Roeland M.H Merks, Ren_e F.M. van Oers, Elisabeth G. Rens

Last modified: 2014-06-09


Apart from molecular signals, mechanical cell-cell communication is key to ex-

plaining the collective cell behavior driving biological morphogenesis. Yet, most

computational models of collective cell behavior focus on chemical signaling.

Endothelial cell cultures on compliant substrates are a good model system of me-

chanical signaling during morphogenesis. Depending on the sti_ness and other

biophysical and chemical properties of the substrates, the endothelial cells can

form blood vessel-like structures, including vascular networks and sprouts. Here

we discuss a hybrid Cellular Potts and _nite element computational model, in

which a limited set of biologically plausible rules describing the mechanical cell-

ECM interactions su_ces for reproducing aspects of endothelial cell behavior

at the single cell, pairwise and collective scale. The model includes the contrac-

tile forces that endothelial cells exert on the ECM, the resulting strains in the

extracellular matrix, and the cellular response to the strains.

The simulations reproduce the behavior of individual endothelial cells, the in-

teractions of endothelial cell pairs in compliant matrices, and network formation

and sprouting from endothelial spheroids. Combining the present, mechanical

model with aspects of previously proposed mechanical and chemical models may

lead to a more complete understanding of angiogenesis and other mechanisms

of morphogenesis.