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

TL;DR

This paper introduces a multiphase continuum model that simulates chemotaxis-driven cell patterning, leading to vascular-like structures in vitro, and analyzes key parameters influencing pattern formation.

Contribution

The study develops a biologically-motivated multiphase model capable of long-term pattern formation in 1D and 2D, incorporating chemoattractant-matrix binding and other mechanisms.

Findings

Chemotaxis can induce cell clustering and vascular-like structures.

Parameter sensitivity analysis identifies key factors influencing pattern formation.

Model reproduces biologically plausible vascular patterns in 1D and 2D.

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. We demonstrate that, within this framework, chemotaxis-driven cell migration can lead to 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 to augment the spatial scale of patterning to within a biologically plausible range. 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.