LAUSR

Significance Modulation of cellular electrophysiology helps develop an understanding of cellular development and function in healthy and diseased states. We modulate the electrophysiology of neuronal cells in two-dimensional (2D) and 3D assemblies with subcellular precision via photothermal stimulation using a multiscale fuzzy graphene nanostructure. Nanowire (NW)-templated 3D fuzzy graphene (NT-3DFG) nanostructures enable remote, nongenetic photothermal stimulation with laser energies as low as subhundred nanojoules without generating cellular stress. NT-3DFG serves as a powerful toolset for studies of cell signaling within and between in vitro 3D models (human-based organoids and spheroids) and can enable therapeutic interventions. The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and between tissues and can enable therapeutic interventions.