Graphene-Mediated Optical Stimulation for Modulation of Neuronal Activity
Alex Savtchenko a, Janaina Sena De Souza b, Andrew Setiadi a, Erin LaMontagne b, Yuhui Li c, Alysson Muotri b, Elena Molokanova a
a Nanotools Bioscience, United States
b University of California San Diego, Gilman Drive, 9500, San Diego, United States
c Cornell University, US, Bard Hall, 214 Ithaca, NY 14850, USA, Ithaca, United States
Proceedings of Light Actuators for Optical Stimulation of Living Systems (LIV-ACT)
Online, Spain, 2022 September 21st - 21st
Organizer: Achilleas Savva
Invited Speaker, Alex Savtchenko, presentation 014
Publication date: 8th September 2022

The ability to probe the activity of neuronal networks can allow deciphering the fundamental processes in the brain and, eventually, help with the diagnosis and treatment of neurological disorders. Optogenetics is currently a leader among optical stimulation methods. However, optogenetic stimulation is a complex phenomenon that inevitably affects cells due to the need for high expression levels of exogenous light-sensitive ion channels, their gating kinetics, and the activity of specific ions conducted by optogenetic actuators. Therefore, in certain cell systems (e.g., stem cell-derived neurons), it is not desirable to express exogenous proteins that might affect physiology of differentiating and maturing cells.

   We pioneered an alternative optical stimulation method that enables fast and reversible optical stimulation of genetically intact neurons by taking advantage of optoelectronic properties of graphene. Previously, graphene materials have been successfully interfaced with various cell types in cell scaffolds, where graphene merely provides the passive structural support. In contrast, in this study, due to its ability to efficiently convert light to electricity, graphene can play an active role in interactions with live cells.

Here we present a novel optoelectrical biointerface for graphene-mediated optical stimulation (GraMOS) of cells via external light-controlled electric field [1]. Our GraMOS biointerface does not interfere with either genetic make-up of cells or their structural integrity, thus providing truly non-invasive stimulation. By performing imaging and electrophysiological experiments on hiPSC-derived neurons, we demonstrated that the GraMOS biointerface exhibits the excellent biocompatibility and the ability to optically trigger action potentials in neurons. Using geometrically patterning of GraMOS biointerfaces, we are evaluating the connectivity of neuronal networks under various experimental conditions. Graphene-mediated optical stimulation is a powerful new method that can be used 1) to probe the existing neuronal activity, decipher the fundamental processes in the brain and, eventually, help with the diagnosis and treatment of neurological disorders; and 2) to elevate the neuronal activity to the new level that could enable activity-dependent neurogenesis, restore vision, and assist with deep-brain stimulation.

This work was supported by NIH grants 1R43TR003252-01A1, 1R43TR001911-01A1, 1R43MH124563-01A1, R21-HL152324, and DISC2-13483 from CIRM.

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