We propose a network representation of electrically coupled beta cells in islets of Langerhans. Beta cells are functionally connected on the basis of correlations between calcium dynamics of individual cells, obtained by means of confocal laser-scanning calcium imaging in islets from acute mouse pancreas tissue slices. Obtained functional networks are analyzed in the light of known structural and physiological properties of islets. Focusing on the temporal evolution of the network under stimulation with glucose, we show that the dynamics are more correlated under stimulation than under non-stimulated conditions and that the highest overall correlation, largely independent of Euclidean distances between cells, is observed in the activation and deactivation phases when cells are driven by the external stimulus. Moreover, we find that the range of interactions in networks during activity shows a clear dependence on the Euclidean distance, lending support to previous observations that beta cells are synchronized via calcium waves spreading throughout islets. Most interestingly, the functional connectivity patterns between beta cells exhibit small-world properties, suggesting that beta cells do not form a homogeneous geometric network but are connected in a functionally more efficient way. Presented results provide support for the existing knowledge of beta cell physiology from a network perspective and shed important new light on the functional organization of beta cell syncitia whose structural topology is probably not as trivial as believed so far. Complex network theory has provided new tools for studying the structure and function of complex systems. A particularly attractive avenue in this context is the analysis of biological systems, since structural principles of complex networks have been identified at all scales of functioning of living organisms. In the present paper, we propose a construction of a complex network representation of pancreatic islets of Langerhans. In this microorgan, interconnected beta cells produce and secrete insulin, an anabolic hormone that controls the level of nutrients in the blood. We determine the functional connectivity on the basis of patterns of correlations between experimentally measured calcium dynamics in individual beta cells. The extracted pattern of pairwise interactions between network elements, i.e. beta cells, is then scrutinized with conventional tools for network analysis. Our findings are largely reconcilable with known structural and functional properties but also point to the presence of unexpected small-world attributes that appear to represent a general organizational principle of the functional connectivity between beta cells. We argue that complex network analysis applied to islets of Langerhans is a valuable new tool in the physiologist's analytical repertoire, and in the future it could help deepen our understanding of their physiology.

Technological advances in imaging techniques and biometric data acquisition have enabled us to apply methods of network science to study the morphology and structural design of organelles, organs, and tissues, as well as the coordinated interactions among them that yield a healthy physiology at the level of whole organisms. We here review research dedicated to these advances, in particular focusing on networks between cells, the topology of multicellular structures, neural interactions, fluid transportation networks, and anatomical networks. The percolation of blood vessels, structural connectivity within the brain, the porous structure of bones, and relations between different anatomical parts of the human body are just some of the examples that we explore in detail. We argue and show that the models, methods, and algorithms developed in the realm of network science are ushering in a new era of network-based inquiry into the morphology and structural design of living systems in the broadest possible terms. We also emphasize that the need and applicability of this research is likely to increase significantly in the years to come due to the rapid progress made in the development of bioartificial substitutes and tissue engineering.

Collective beta cell activity in islets of Langerhans is critical for the supply of insulin within an organism. Even though individual beta cells are intrinsically heterogeneous, the presence of intercellular coupling mechanisms ensures coordinated activity and a well-regulated exocytosis of insulin. In order to get a detailed insight into the functional organization of the syncytium, we applied advanced analytical tools from the realm of complex network theory to uncover the functional connectivity pattern among cells composing the intact islet. The procedure is based on the determination of correlations between long temporal traces obtained from confocal functional multicellular calcium imaging of beta cells stimulated in a stepwise manner with a range of physiological glucose concentrations. Our results revealed that the extracted connectivity networks are sparse for low glucose concentrations, whereas for higher stimulatory levels they become more densely connected. Most importantly, for all ranges of glucose concentration beta cells within the islets form locally clustered functional sub-compartments, thereby indicating that their collective activity profiles exhibit a modular nature. Moreover, we show that the observed non-linear functional relationship between different network metrics and glucose concentration represents a well-balanced setup that parallels physiological insulin release.