Molecular Machines Enhance Insulin Release in Pancreatic Beta Cells

The production and secretion of insulin by pancreatic beta cells plays a critical role in glucose homeostasis. Insulin signaling dysfunction typically results in diabetes mellitus, which affects over 415 million people worldwide. The development of new tools to induce insulin secretion in individual cells would enable the study of the cellular processes involved during insulin secretion, facilitating the discovery of new treatments for diabetes mellitus. Here, we demonstrate a transgene-free photomechanical modality for single-cell modulation of pancreatic beta cells. Pancreatic beta cells treated with fast, unidirectionally rotating molecular motors (MM) responded to pulses of visible light with the release of calcium from the endoplasmic reticulum by inositol trisphosphate (IP₃)-mediated signaling. In the presence of extracellular glucose, this effect enhanced calcium spiking in pancreatic beta cell colonies. Cell populations treated with MM and light demonstrated enhanced exocytosis compared to cells treated with light alone. These results demonstrate the ability of a molecular mechanical actuator to amplify exocytosis in pancreatic beta cells by manipulating intracellular calcium. This could lead to new strategies for studying insulin dysfunction in diabetes, as well as for controlling calcium-sensitive endocrine signaling with molecular-scale mechanical devices.