Biomedical Engineering Reference
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Fig. 6 Morphospace of proteolytic enzyme secretion by stalk cells. Tip and stalk cells secrete
u-PA and MMP to degrade fibrin and the basement membrane respectively. The secretion of u-PA
and MMP by stalk cells is expressed in percentage of the maximal secretion rate as secreted by the
tip cell. This results in different sprout morphologies: sprouts (a), solid cyst-like structures (b),
hollow cyst-like structures (c) and monolayers (d)
isolated from unfractionated fibrin and used to create different densities of the
matrix. A matrix composed of only LMW fibrinogen has thinner fibers and has a
denser structure than a matrix made from only HMW fibrinogen (Fig.
7
). Small
differences in fibrin matrix lead to different gene expression patterns in endothelial
cells [
44
] and influence tube formation [
47
]. Tube formation was more extensive
in HMW than in LMW matrices. We plan to use the computational model to
examine how these differences in matrix structure influence sprouting.
3.3 Modeling Perspectives
Koolwijk et al. developed an in vitro model to examine tube formation in angi-
ogenesis [
1
]. To gain knowledge in the mechanism and key players involved, we
created a computational model that resembles the experimental in vitro model. The
computational model is used to validate conceptual models for basic mechanisms
of sprouting and to predict how alterations in cell behavior will affect sprouting.
The model explains experimental observations concerning the effects of proteo-
lytic enzyme activity on sprout morphology by supporting the hypothesis that not
only the level, but also the distribution of proteolytic enzyme secretion over tip and
stalk cells is responsible for different sprout morphologies. Several experimental
observations and techniques can help to validate conclusions drawn from the
model.
Contradictions
between
experimental
data
and
the
computational
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