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

Math Biosci. 2024 Jun:372:109183. doi: 10.1016/j.mbs.2024.109183. Epub 2024 Mar 28.

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.

MeSH terms

  • Cell Movement / physiology
  • Chemotaxis* / physiology
  • Computer Simulation
  • Extracellular Matrix* / metabolism
  • Extracellular Matrix* / physiology
  • Humans
  • Models, Biological*