Formation of vascular-like structures using a chemotaxis-driven multiphase model

Abstract

We propose a continuum model for pattern formation, based on the multiphase model framework, to explore in vitro cell patterning within an extracellular matrix (ECM). We demonstrate that, within this framework, chemotaxis-driven cell migration can lead to the formation of cell clusters and vascular-like structures in 1D and 2D respectively. The influence on pattern formation of additional mechanisms commonly included in multiphase tissue models, including cell-matrix traction, contact inhibition, and cell–cell aggregation, are also investigated. Using sensitivity analysis, the relative impact of each model parameter on the simulation outcomes is assessed to identify the key parameters involved. Chemoattractant–matrix binding is further included, motivated by previous experimental studies, and found to reduce the spatial scale of patterning to within a biologically plausible range for capillary structures. Key findings from the in-depth parameter analysis of the 1D models, both with and without chemoattractant–matrix binding, are demonstrated to translate well to the 2D model, obtaining vascular-like cell patterning for multiple parameter regimes. Overall, we demonstrate a biologically-motivated multiphase model capable of generating long-term pattern formation on a biologically plausible spatial scale both in 1D and 2D, with applications for modelling in vitro vascular network formation.