4 research outputs found
Network formation of tissue cells via preferential attraction to elongated structures
Vascular and non-vascular cells often form an interconnected network in
vitro, similar to the early vascular bed of warm blooded embryos. Our
time-lapse recordings show that the network forms by extending sprouts, i.e.,
multicellular linear segments. To explain the emergence of such structures, we
propose a simple model of preferential attraction to stretched cells. Numerical
simulations reveal that the model evolves into a quasi-stationary pattern
containing linear segments, which interconnect above the critical volume
fraction of 0.2. In the quasi-stationary state the generation of new branches
offset the coarsening driven by surface tension. In agreement with empirical
data, the characteristic size of the resulting polygonal pattern is
density-independent within a wide range of volume fractions
Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth
Blood vessels form either when dispersed endothelial cells (the cells lining
the inner walls of fully-formed blood vessels) organize into a vessel network
(vasculogenesis), or by sprouting or splitting of existing blood vessels
(angiogenesis). Although they are closely related biologically, no current
model explains both phenomena with a single biophysical mechanism. Most
computational models describe sprouting at the level of the blood vessel,
ignoring how cell behavior drives branch splitting during sprouting. We present
a cell-based, Glazier-Graner-Hogeweg-model simulation of the initial patterning
before the vascular cords form lumens, based on plausible behaviors of
endothelial cells. The endothelial cells secrete a chemoattractant, which
attracts other endothelial cells. As in the classic Keller-Segel model,
chemotaxis by itself causes cells to aggregate into isolated clusters. However,
including experimentally-observed adhesion-driven contact inhibition of
chemotaxis in the simulation causes randomly-distributed cells to organize into
networks and cell aggregates to sprout, reproducing aspects of both de novo and
sprouting blood-vessel growth. We discuss two branching instabilities
responsible for our results. Cells at the surfaces of cell clusters attempting
to migrate to the centers of the clusters produce a buckling instability. In a
model variant that eliminates the surface-normal force, a dissipative mechanism
drives sprouting, with the secreted chemical acting both as a chemoattractant
and as an inhibitor of pseudopod extension. The branching instabilities
responsible for our results, which result from contact inhibition of
chemotaxis, are both generic developmental mechanisms and interesting examples
of unusual patterning instabilities.Comment: Thoroughly revised version, now in press in PLoS Computational
Biology. 53 pages, 13 figures, 2 supporting figures, 56 supporting movies,
source code and parameters files for computer simulations provided.
Supporting information: http://www.psb.ugent.be/~romer/ploscompbiol/ Source
code: http://sourceforge.net/projects/tst