Protein‐Template Gold Nanoclusters Induce Differentiation and Modify the Functional Properties of Primary Astrocytes

Astrocyte ion channels, water channels, and calcium signaling play vital roles in maintaining brain homeostasis, coordinating neural network activity, supporting cognitive functions, and mediating neurovascular coupling. Disruptions in astrocyte dynamics are causally linked to gliosis occurring in pathologies, such as brain injuries and neurological diseases. Despite their importance, the potential to probe and modulate astrocyte molecular, functional, and morphological properties using intracellular light adsorbing nanoscale interfaces has been limited. In this study, we investigate the effects of fluorescent gold nanoclusters (fAuNCs) bound to bovine serum albumin (BSA) on the morphological, molecular, and functional properties of primary rat cortical astrocytes over an extended period. Treatment with fAuNCs‐BSA is not toxic over long term and induces notable morphological changes alongside alterations in whole‐cell chloride currents, cell volume regulation, and calcium signaling magnitude. To leverage the light‐absorbing properties of fAuNCs‐BSA, we expose acutely fAuNCs‐BSA‐treated astrocytes to LED blue light (λ_ex = 450 nm), which modulates potassium currents. Nanodiamond thermometry suggests that this effect results from local heating caused by photoexcitation of the nanoclusters. The potential of nanoclusters as a transformative approach for studying astrocyte function and their role in the biophysical mechanisms underlying neural communication is discussed.