# Random matrix analysis of Ca$^{2+}$ signals in $\beta$-cell collectives

## TL;DR

This study applies random matrix theory to analyze calcium signaling in pancreatic beta-cell collectives, revealing how heterogeneity influences collective dynamics and responses to glucose stimulation.

## Contribution

It introduces a novel application of RMT to characterize functional heterogeneity in beta-cell collectives and distinguish physiological states based on spectral properties.

## Key findings

- Empirical eigenvalue spectra mostly match RMT predictions.
- Deviating eigenvalues indicate local and extended modes of correlation.
- Number variance can differentiate stimulated from non-stimulated conditions.

## Abstract

Even within small organs like pancreatic islets, different endocrine cell types and subtypes form a heterogeneous collective to sense the chemical composition of the extracellular solution and compute an adequate hormonal output. Erroneous cellular processing and hormonal output due to challenged heterogeneity result in various disorders with diabetes mellitus as a flagship metabolic disease. Here we attempt to address the aforementioned functional heterogeneity with comparing pairwise cell-cell cross-correlations obtained from simultaneous measurements of cytosolic calcium responses in hundreds of islet cells in an optical plane to statistical properties of correlations predicted by the random matrix theory (RMT). We find that the bulk of the empirical eigenvalue spectrum is almost completely described by RMT prediction, however, the deviating eigenvalues that exist below and above RMT spectral edges suggest that there are local and extended modes driving the correlations. We show that empirical nearest neighbor spacing of eigenvalues follows universal RMT properties regardless of glucose stimulation, but that number variance displays clear separation from RMT prediction and can differentiate between empirical spectra obtained under non-stimulated and stimulated conditions. We suggest that RMT approach provides a sensitive tool to assess the functional cell heterogeneity and its effects on the spatio-temporal dynamics a collective of beta cells in pancreatic islets in physiological resting and stimulatory conditions.