Dimensionality and Size Scaling of Coordinated Ca²⁺ Dynamics in MIN6 尾-cell Clusters

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• 作者：Thomas聽H. Hraha ; Abigail聽B. Bernard ; Linda聽M. Nguyen ; Kristi聽S. Anseth ; Richard聽K.P. Benninger
• 刊名：Biophysical Journal
• 出版年：7 January, 2014
• 年：2014
• 卷：106
• 期：1
• 页码：299-309
• 全文大小：1819 K

文摘

Pancreatic islets of Langerhans regulate blood glucose homeostasis by the secretion of the hormone insulin. Like many neuroendocrine cells, the coupling between insulin-secreting 尾-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 尾-cell line with defined sizes and dimensions. We measured the dynamics of free-calcium activity ([Ca²⁺]_i) and insulin secretion and compared these measurements with a percolating network model. We observed that the coupling dimension was critical for regulating [Ca²⁺]_i dynamics and insulin secretion. Three-dimensional coupling led to size-invariant suppression of [Ca²⁺]_i at low glucose and robust synchronized [Ca²⁺]_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 [Ca²⁺]_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 尾-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.