Biomedical Engineering Reference
In-Depth Information
properties and behaviors determine the dynamics of tube formation. We aim to
extend this model to a multi-scale model in the sense that cells, extracellular
matrix and cell-regulation are described at different levels of detail and feedback
on each other. Finally we discuss how computational modeling, combined with in
vitro and in vivo modeling steers experiments, and how it generates new experi-
mental hypotheses and insights on the mechanics of angiogenesis.
1 Introduction
Blood vessel growth is essential during embryogenesis, but is also a prominent
aspect of diseases such as cancer, rheumatoid arthritis and retinopathy. Angio-
genesis research can benefit from computational models in three ways. Firstly,
computational models help to gain an overview in this complex system by testing
which components and interactions are minimally required. These components and
interactions can then be examined to understand their function and predict their
effects. Computational models are therefore not only useful to gain mechanistic
understanding of angiogenesis, but also to find new therapeutic targets. Secondly,
computational models can discriminate between and select from alternative
hypotheses. Often, more than one hypothesis explains a biological observation,
such as network formation from dispersed endothelial cells. Computational models
can test the sufficiency of each hypotheses to reproduce the biological observa-
tions. Predictions that result from these models can be validated experimentally to
support or reject the tested hypotheses. Thirdly, computational models can connect
and combine knowledge on single proteins and mechanisms to examine angio-
genesis as a system. Experimental research is often limited to a specific step or
protein in angiogenesis and does not grasp how this part is integrated in the whole.
Ultimately, computational models include processes at multiple scales, like
extracellular matrix, cells, and cell-regulation simultaneously. Such multi-scale
models are the next step in computational modeling to make the transition to
angiogenesis in the body.
In the first section, computational models of network formation and sprouting
are reviewed. These models address questions that have been raised by experi-
mental observations and thereby give new insights in angiogenesis. It concludes by
discussing the current state of multi-scale modeling. The next section gives a
practical example of how computational models can be used in angiogenesis
research and shows how systems biology, a continuous cooperation between
computational and experimental biologists, drives development of computational
models. To do so, we introduce a new computational model of sprouting, based on
an experimental model of capillary-like tube formation by Koolwijk et al. [ 1 ].
Finally we will discuss which steps should be taken in angiogenesis research to
further evolve computational modeling.
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