Last modified: 2014-06-09
Abstract
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.