Modeling Polarity-Driven Laminar Patterns in Bilayer Tissues with Mixed Signaling Mechanisms

Abstract

Recent advances in high-resolution experimental methods have highlighted the significance of cell signal pathway crosstalk and localized signaling 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 signaling, which generates both a spatial and a temporal dependence on cell behaviors. Motivated by cellular mechanisms that control cell-fate decisions in developing bilayer tissues, we use dynamical systems coupled with multilayer graphs to analyze the role of signaling polarity and pathway crosstalk in fine-grain pattern formation of protein activity. Specifically, we study how multilayer graph edge structures and weights influence the layerwise (laminar) patterning of cells in bilayer structures, which are commonly found in glandular tissues. We present sufficient conditions for the 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.