Tunability of Calcium Dynamics by Signaling Inputs and Cell-cell Communication in Pancreatic Beta Cells

Date of Award

Spring 1-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular Biophysics and Biochemistry

First Advisor

Levchenko, Andre

Abstract

In addition to frequently occurring stable all-or-none responses, live cells can display more complex response dynamics, e.g., oscillations in the activity/concentration of biomolecules. Although the emergence and the function of oscillatory dynamics have been heavily investigated, fewer efforts have been spent on whether cells can fine-tune different aspects of an oscillatory signal (e.g. peak width, duty cycle, and frequency) and whether this fine-tuning can allow oscillatory signals to convey an extra layer of information. This thesis investigates glucose-induced calcium (Ca2+) dynamics in MIN6 cells, a model cell line for pancreatic beta cells, and reveals that the spontaneous or induced changes in the phosphatidylinositol 4,5-bisphosphate (PIP2) level can diversify Ca2+ dynamics by modulating peak widths of Ca2+ spikes. Additionally, a combination of optogenetics and Ca2+ imaging demonstrates that variations in the widths and frequencies of Ca2+ spikes can strongly influence the coupling between neighboring MIN6 cells. Finally, a model is proposed where pancreatic beta cells can utilize the ability to modulate and communicate through Ca2+ peak widths to achieve labor division in fine-tuning insulin release.

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