Electrical Stimulation by an Organic Transistor Architecture Induces Calcium Signaling in Nonexcitable Brain Cells

Abstract

materialsdisplay intrinsic multi functionality, combining ionoelectronic transport properties, photonic properties, and optical transparency within the visible range with improved biocompatibility with neural cells compared to inorganic sub strates. [1][2][3][4] Notably, the survival of primary neuronal cells on organic bioelectronic polymers [1,3,4] and small molecules [5,6] is higher when compared to silicon/glass substrates, while the functionality of brain cells is preserved on organic biofunctional interfaces. [1,5] Importantly, organic bioelec tronic [3,7] and biooptoelectronic [8,9] devices capable to record, stimulate, and modulate functionality of neuronal cells in vitro [7] and in vivo [3] have been reported, showing the potential and the relevance for clinical neurology as well as for neuroscience fun damental studies.Recently, the role of glial cells, called astrocytes, is emerging among the chal lenges and targets that need to be con sidered for the development of devices devoted to neuroscience investigations and applications. Astrocytes are, indeed, the cells that are majorly involved in the regulation of the concentration of ions and neu rotransmitters in the synaptic cleft, participating to communica tion signals between neurons and playing a pivotal role in the brain physio logy. [10,11] The function of astrocytes mainly depends on the activity of transmembrane proteins forming transporters, Organic bioelectronics have a huge potential to generate interfaces and devices for the study of brain functions and for the therapy of brain pathologies. In this context, increasing efforts are needed to develop technologies for monitoring and stimulation of nonexcitable brain cells, called astrocytes. Astroglial calcium signaling plays, indeed, a pivotal role in the physiology and pathophysiology of the brain. Here, the use of transparent organic cell stimulating and sensing transistor (O-CST) architecture, fabricated with N,N′-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (P13), to elicit and monitor intracellular calcium concentration ([Ca 2+ ] i ) in primary rat neocortical astrocytes is demonstrated. The transparency of O-CST allows performing calcium imaging experiments, showing that extracellular electrical stimulation of astrocytes induces a drastic increase in [Ca 2+ ] i . Pharmacological studies indicate that transient receptor potential (TRP) superfamily are critical mediators of the [Ca 2+ ] i increase. Experimental and computational analyses show that [Ca 2+ ] i response is enabled by the O-CST device architecture. Noteworthy, the extracellular field application induces a slight but significant increase in the cell volume. Collectively, it is shown that the O-CST is capable of selectively evoking astrocytes [Ca 2+ ] i , paving the way to the development of organic bioelectronic devices as glial interfaces to excite and control physiology of non-neuronal brain cells.

A Glial‐Silicon Nanowire Electrode Junction Enabling Differentiation and Noninvasive Recording of Slow Oscillations from Primary Astrocytes

“…To date, extracellular recording systems based on planar microelectrode arrays (MEAs) are the optimal electrophysiological equipment for noninvasive long‐term analysis studying of neuronal circuit‐connectivity in vitro and in vivo 7. While stimulation of astrocytes signaling has been achieved successfully with organic field effect transistor devices, the use of MEA for the recording of astroglial cells signaling in vitro still displayed critical issues 8–10. First, astrocyte primary cultures, grown on flat substrates lose structural and functional features,11a,b,12 essential for their homeostatic and physiological function in vivo 13.…”

Stimulation of water and calcium dynamics in astrocytes with pulsed infrared light

“…We have recently demonstrated that it is possible to evoke astrocytic Ca2+ responses mediated by TRPV4, TRPA1 as well as cell swelling with electrical stimulation 21 by organic cell stimulating and sensing device. Previous attempts from other groups to evoke astrocytic Ca 2+ responses with light in cell cultures were only successful when used with cell‐conjugated NIR‐optimized plasmonic nanostructures or label‐free with high‐intensity ultrafast NIR laser pulses 56‐58 .…”

“…Methods to study astrocytic processes have been for a long time confined to conventional pharmacology, genetic manipulation, fluorescence imaging of molecular sensors, and electrophysiology 3,5,11,14,17‐19 . More recently, we demonstrated that it is possible to evoke chloride ion conductances, 20 astrocytic Ca2+ responses mediated by TRPV4 and cell swelling by optical or electrical stimulation operated by organic devices 21 . Optical tools can provide precise, fast, label‐free control of ions, and water dynamics to study the cellular and molecular mechanisms of astrocytes function and to potentially treat dysfunction.…”

“…Optical tools can provide precise, fast, label‐free control of ions, and water dynamics to study the cellular and molecular mechanisms of astrocytes function and to potentially treat dysfunction. However, despite recent advances in optogenetics approaches and optoelectronics device to study neurons, 22,23 there is a continued need for reliable methods for label‐free control of ion flux and water dynamics in astrocytes 19,21,22,24 …”

Glial Interfaces: Advanced Materials and Devices to Uncover the Role of Astroglial Cells in Brain Function and Dysfunction

“…Among small molecule organic semiconductors, perylene dimmide derivative N, N'-ditridecylperylene-3,4,9,10tetracarboxylic diimide (P13), has been shown to be biocompatible with rat primary astrocytes in vitro. [114] In a recent work, it is shown that transparent organic cell stimulating and sensing transistor (O-CST) architecture, fabricated with P13, [115] was used to explore the impact of field effect extracellular stimulation on intracellular calcium concentration ([Ca 2+ ] i ) in primary rat neocortical astrocytes. Calcium imaging experiments enabled by the transparency of O-CST showing that a slow rise in extracellular potential between the gate and the grounded source electrodes provide an effective extracellular electrical stimulation of astrocytes that induces a slow and persistent increase in astrocytic [Ca 2+ ] i .…”