Autopoietic influence hierarchies in pancreatic $β$-cells

Abstract

$β$-cells are biologically essential for humans and other vertebrates. Because their functionality arises from cell-cell interactions, they are also a model system for collective organization among cells. There are currently two contradictory pictures of this organization: the hub-cell idea pointing at leaders who coordinate the others, and the electrophysiological theory describing all cells as equal. We use new data and computational modeling to reconcile these pictures. We find via a network representation of interacting $β$-cells that leaders emerge naturally (confirming the hub-cell idea), yet all cells can take the hub role following a perturbation (in line with electrophysiology). A useful network representation of complex systems is via pairwise cross-correlations between a system's constituents. Recently, attempts have been made at representing pancreatic $β$-cells collectives as networks, giving birth to the concept of hub cells, which contradicts established electrophysiological theory. Here, we reconcile the hub-cell idea with electrophysiology using empirical and computational methods. While the former reveals the functional importance of hubs, the latter show that hubs are an emergent property of communication among identical peers. Thus, individual cells are perfectly capable of playing the hub role, but in line with electrophysiology, they do not have to be genetically predisposed to do so. This points to an ultra-robust architecture of $β$-cell collectives and underpins some of their vital features.