Modelling polarity-driven laminar patterns in bilayer tissues with mixed signalling mechanisms

TL;DR

This paper develops a mathematical framework using multilayer graphs and dynamical systems to understand how cell signalling polarity influences fine-grain laminar pattern formation in bilayer tissues, relevant to development and disease.

Contribution

It introduces a novel approach combining graph theory and dynamical systems to analyze polarity-driven patterning in bilayer tissues, providing conditions for pattern existence and convergence.

Findings

Derived conditions for homogeneous state stability and pattern formation.

Linked spectral properties of graph structures to pattern convergence.

Validated the approach for large-scale tissue models.

Abstract

Recent advances in high-resolution experimental methods have highlighted the significance of cell signal pathway crosstalk and localised signalling activity in the development and disease of numerous biological systems. The investigation of multiple signal pathways often introduces different methods of cell-cell communication, i.e. contact-based or diffusive signalling, which generates both a spatial and temporal dependence on cell behaviours. Motivated by cellular mechanisms that control cell-fate decisions in developing bilayer tissues, we use dynamical systems coupled with multilayer graphs to analyse the role of signalling polarity and pathway crosstalk in fine-grain pattern formation of protein activity. Specifically, we study how multilayer graph edge structures and weights influence the layer-wise (laminar) patterning of cells in bilayer structures, which are commonly found in glandular tissues. We present sufficient conditions for existence, uniqueness and instability of homogeneous cell states in the large-scale spatially discrete dynamical system. Using methods of pattern templating by graph partitioning to generate quotient systems in combination with concepts from monotone dynamical systems, we exploit the extensive dimensionality reduction to provide existence conditions for the polarity required to induce fine-grain laminar patterns with multiple spatially dependent intracellular components. We then explore the spectral links between the quotient and large-scale dynamical systems to extend the laminar patterning criteria from existence to convergence for sufficiently large amounts of cellular polarity in the large-scale dynamical system, independent of spatial dimension and number of cells in the tissue.