Modeling the early stages of vascular network assembly

Abstract

contributed equally to this workIn vertebrates, networks of capillary vessels supply tissues with nutrients. Capillary patterns are closely mimicked by endothelial cells cultured on basement membrane proteins that allow single randomly dispersed cells to self-organize into vascular networks.Here we provide a model including chemoattraction as the fundamental mechanism for cell-to-cell communication in order to identify key parameters in the complexity of the formation of vascular patterns. Bȳ anking biological experiments, theoretical insights and numerical simulations, we provide strong evidence that endothelial cell number and the range of activity of a chemoattractant factor regulate vascular network formation and size. We propose a mechanism linking the scale of formed endothelial structures to the range of cell-to-cell interaction mediated by the release of chemoattractants.

Modeling Morphogenesisin silicoandin vitro: Towards Quantitative, Predictive, Cell-based Modeling

“…They developed a series of continuum models [2,48,15] whose results they compared to HUVEC-Matrigel cultures. The Preziosi model assumes that a) endothelial cells secrete a chemoattractant which attracts other endothelial cells, b) the chemoattractant diffuses in the extracellular matrix which gradually inactivates it, and c) endothelial cell motion is direction persistent.…”

A simple mechanistic model of sprout spacing in tumour-associated angiogenesis

“…The decay rate reported by Serini et al (2003) is large enough to make a significant difference to our analysis. With g40, the expression for activator concentration, Eq.…”

“…An estimate for the value of the decay coefficient, l a , has been calculated from an in vitro halflife of VEGF, found by Serini et al (2003) to be 64 AE 7min. Behaviour of the model for a range of decay rates around this value has been investigated and is discussed in Section 5.…”

“…4. Steady state non-dimensionalised activator levels (log scale) vs non-dimensionalised distance along limbus, r, for three different decay rates, g s (light line), g s =2 (dotted line), and 2g s (heavy line), where g s is the non-dimensionalised version of the decay rate given in Serini et al (2003). The dashed vertical line may be used to find steady state values at a distance along the limbus equal to 0:6 of the distance from tumour to limbus.…”

Individual cell-based models of cell scatter of ARO and MLP-29 cells in response to hepatocyte growth factor

“…It is necessary to add a term related to cell polarization and persistence, in conjunction with a chemotactic response, which were shown to be key ingredients also in the formation of vascular networks [10,25,28].…”