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Biophys J. 2014 Jan 7;106(1):299-309. doi: 10.1016/j.bpj.2013.11.026.

Dimensionality and size scaling of coordinated Ca(2+) dynamics in MIN6 β-cell clusters.

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Department of Bioengineering, University of Colorado, Anschutz Medical campus, Aurora, CO.
Department of Biological and Chemical Engineering and the Howard Hughes Medical Institute, University of Colorado, Boulder, CO.
Department of Bioengineering, University of Colorado, Anschutz Medical campus, Aurora, CO; Barbara Davis Center for Childhood Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, CO. Electronic address:


Pancreatic islets of Langerhans regulate blood glucose homeostasis by the secretion of the hormone insulin. Like many neuroendocrine cells, the coupling between insulin-secreting β-cells in the islet is critical for the dynamics of hormone secretion. We have examined how this coupling architecture regulates the electrical dynamics that underlie insulin secretion by utilizing a microwell-based aggregation method to generate clusters of a β-cell line with defined sizes and dimensions. We measured the dynamics of free-calcium activity ([Ca(2+)]i) and insulin secretion and compared these measurements with a percolating network model. We observed that the coupling dimension was critical for regulating [Ca(2+)]i dynamics and insulin secretion. Three-dimensional coupling led to size-invariant suppression of [Ca(2+)]i at low glucose and robust synchronized [Ca(2+)]i oscillations at elevated glucose, whereas two-dimensional coupling showed poor suppression and less robust synchronization, with significant size-dependence. The dimension- and size-scaling of [Ca(2+)]i at high and low glucose could be accurately described with the percolating network model, using similar network connectivity. As such this could explain the fundamentally different behavior and size-scaling observed under each coupling dimension. This study highlights the dependence of proper β-cell function on the coupling architecture that will be important for developing therapeutic treatments for diabetes such as islet transplantation techniques. Furthermore, this will be vital to gain a better understanding of the general features by which cellular interactions regulate coupled multicellular systems.

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