Self-organization of self-clearing beating patterns in an array of locally interacting ciliated cells formulated as an adaptive Boolean network

The observed spatiotemporal ciliary beat patterns leading to proper mucociliary clearance on multiciliated epithelia are suspected to be the result of self-organizing processes on various levels. Here, we present a simplified pluricellular epithelium model, which intends to make the self-organization of ciliary beating patterns as well as of the associated fluid transport across the airway epithelium plausible. The model is based on a two-dimensional array of locally interacting oscillating ciliated cells. Ciliated cells are represented by Boolean actuators, and abstracted hydrodynamic mucociliary interactions are formulated in terms of logical update rules (Boolean functions). In the course of a simulation, initial random conformations of an array of actuators self-organize toward metachronally coordinated states exhibiting efficient transport of mucus. Within the framework of Boolean networks ciliated cells represent the nodes of the network and as the mucus establishes the local interactions among nodes, its distribution (together with the formulated local interactions) determines the topology of the network. Consequently, we propose to consider the dynamics on multiciliated epithelia in the context of adaptive (Boolean) networks. Furthermore, we would like to present insights gained from conducted comprehensive parameter studies. In particular, the dynamical response of the network with respect to variations of the boundary conditions, updating schemes (representing intercellular signaling mechanisms) and the proportion of ciliated cells is presented. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12064-019-00299-x) contains supplementary material, which is available to authorized users.