title: Dimensionality and size scaling of coordinated Ca(2+) dynamics in MIN6 β-cell clusters.
abstract: 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.
authors.affiliation: Department of Bioengineering, University of Colorado, Anschutz Medical campus, Aurora, CO.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hraha
authors.affiliation: Department of Biological and Chemical Engineering and the Howard Hughes Medical Institute, University of Colorado, Boulder, CO.
authors.forename: Abigail B
authors.initials: AB
authors.lastname: Bernard
authors.affiliation: Department of Bioengineering, University of Colorado, Anschutz Medical campus, Aurora, CO.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Nguyen
authors.affiliation: Department of Biological and Chemical Engineering and the Howard Hughes Medical Institute, University of Colorado, Boulder, CO.
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
authors.affiliation: 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: richard.benninger@ucdenver.edu.
authors.forename: Richard K P
authors.initials: RK
authors.lastname: Benninger
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D005089:Exocytosis; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological
chemical_list: D007328:Insulin; D005947:Glucose; D002118:Calcium