Hybrid-nanomaterials for non-genetic optical stimulation of excitable cells

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Electrical stimulation of tissue and ultimately individual cells has not only played an essential role in our understanding of the structure and function of excitable tissue but continues to serve as the basis for a variety of therapeutic interventions for the treatment of disorders ranging from cardiac arrhythmias to Parkinson’s disease. Advances in technology have attempted to overcome barriers associated with the spatial resolution (i.e., who and where to stimulate) and the invasiveness of the process. Optogenetics has revolutionized the way we can record and affect the electrophysiology of cells and tissue, using light as the input/output (I/O) interface. Though optogenetics has developed at a great pace and is making profound scientific contributions, the core of the technique requires genetic modification of the cells or organism (that may affect cellular homeostasis). This presents challenges both in terms of achieving targeted gene expression and the potential deleterious consequences of the expression of foreign proteins, which have implications on clinical translation to humans and regulatory approval. Photostimulation using Au and Si-based nanomaterials has shown promise for non- genetic remote stimulation of cells, using light to trigger highly-localized heating. However, these methods still suffer from key limitations including the need for relatively high laser power due to low absorption cross-section, low thermal conversion efficiency, and unproven long-term stability. Base on the fact that transient capacitive or Faradaic currents due to either photothermal or photoelectrical effects will result with membrane depolarization (excitation) or hyperpolarization (inhibition), we propose to develop and study a breakthrough hybrid- nanomaterial synthesis process to enable minimally-invasive, remote and non-genetic light-induced control of targeted cell activity with high spatial-temporal resolution. To do so, we will combine one-dimensional (1D) nanowires (NWs) and two-dimensional (2D) graphene flakes grown out-of-plane with tailor-made physical properties for highly-controlled photostimulation through either photothermal or photoelectrical processes. Our non-genetic NW templated 3D fuzzy graphene (NT-3DFG) platform will add a powerful tool to the basic scientists studying cell signaling within and between tissues, obviating the need for slow and expensive breeding protocols and/or the screening of viral serotypes to enable the use of light to control cell activity. As we continue to struggle to understand the cells and circuits involved in health and disease, our approach to controlling cell excitability has the potential to accelerate knowledge generation as well as the identification of novel therapeutic targets. In addition to the knowledge generated, this technology should replace the current wire electrode-based approaches for the treatment of diseases ranging from chronic pain to Parkinson’s disease. Last, this platform can be adapted to address challenges in tissue engineering, i.e. the much-needed non-genetic stimulation control of engineered tissues. By controlled delivery of the NT-3DFG we will be able to locally and selectively control cellular activity with high spatial and temporal resolution of 3D tissues.