Causal interaction of metabolic oscillations in monolayers of Hela cervical cancer cells: emergence of complex networks

Abstract

Abstract A novel global cooperative phenomenon was observed in monolayers of HeLa cervical cancer cells that exhibited glycolytic oscillations but did not exhibit synchronisation or partial synchronisation. The analysis of causality of the oscillations between cell pairs in the cell-monolayer sheet revealed a hidden causal interaction network. Furthermore, the network exhibits characteristics of a broad-scale network. This suggests that key cells perform a hub-like function in the network and that the population of HeLa cells forms metabolically connected functional network rather than randomly connected one. Unlike previous work that focused on the synchronisation of glycolytic oscillations in the HeLa cells, the present study analysed the causality between the oscillating cells by Convergent Cross Mapping (CCM), which is based on the phase-space reconstruction of time-series data and is used to find causality in weakly coupled components of nonlinear dynamical systems. We believe that the framework proposed in this study is useful for investigating the hidden state of a group of cells and can accelerate studies on cellular metabolic phenomena including metabolic oscillations in $$\:\beta\:$$ cells within islets of Langerhans. It would also be applicable to systems of weakly coupled oscillators that may include hidden cooperative phenomena.