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

Georgina Al-Badri; James B Phillips; Rebecca J Shipley; Nicholas C Ovenden

doi:10.1016/j.mbs.2024.109183

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

Math Biosci. 2024 Mar 28:372:109183. doi: 10.1016/j.mbs.2024.109183. Online ahead of print.

Authors

Georgina Al-Badri¹, James B Phillips², Rebecca J Shipley³, Nicholas C Ovenden⁴

Affiliations

¹ Department of Mathematics, University College London, London, UK; Centre for Nerve Engineering, University College London, London, UK. Electronic address: georgina.al-badri@ucl.ac.uk.
² Centre for Nerve Engineering, University College London, London, UK; Department of Pharmacology, University College London, London, UK.
³ Centre for Nerve Engineering, University College London, London, UK; Department of Mechanical Engineering, University College London, London, UK.
⁴ Department of Mathematics, University College London, London, UK; Centre for Nerve Engineering, University College London, London, UK.

PMID: 38554855
DOI: 10.1016/j.mbs.2024.109183

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.

Keywords: Chemotaxis; Multiphase modelling; Tissue engineering; Vasculogenesis.