Modeling Morphogenesis in silico and in vitro: Towards Quantitative, Predictive, Cell-based Modeling

¹ CWI, Science Park 123, 1098 XG Amsterdam
² NCSB-NISB, Science Park 904, 1098 XH Amsterdam
³ Laboratory for Physiology, Institute for Cardiovascular Research VU University Medical Center, 1081 BT Amsterdam

Corresponding author: roeland.merks@sysbio.nl

Abstract

Cell-based, mathematical models help make sense of morphogenesis—i.e. cells organizing into shape and pattern—by capturing cell behavior in simple, purely descriptive models. Cell-based models then predict the tissue-level patterns the cells produce collectively. The first step in a cell-based modeling approach is to isolate sub-processes, e.g. the patterning capabilities of one or a few cell types in cell cultures. Cell-based models can then identify the mechanisms responsible for patterning in vitro. This review discusses two cell culture models of morphogenesis that have been studied using this combined experimental-mathematical approach: chondrogenesis (cartilage patterning) and vasculogenesis (de novo blood vessel growth). In both these systems, radically different models can equally plausibly explain the in vitro patterns. Quantitative descriptions of cell behavior would help choose between alternative models. We will briefly review the experimental methodology (microfluidics technology and traction force microscopy) used to measure responses of individual cells to their micro-environment, including chemical gradients, physical forces and neighboring cells. We conclude by discussing how to include quantitative cell descriptions into a cell-based model: the Cellular Potts model.