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The brain integrates activity across networks of interconnected neurons to generate behavioral outputs. Several physiological and imaging-based approaches have been previously used to monitor responses of individual neurons. While these techniques can identify cellular responses greater than the neuron's action potential threshold, less is known about the events that are smaller than this threshold or are localized to subcellular compartments. Here we use NEAs to obtain temporary intracellular access to neurons allowing us to record information-rich data that indicates action potentials, and sub-threshold electrical activity. We demonstrate these recordings from primary hippocampal neurons, induced pluripotent stem cell-derived (iPSC) neurons, and iPSC-derived brain organoids. Moreover, our results show that our arrays can record activity from subcellular compartments of the neuron. We suggest that these data might enable us to correlate activity changes in individual neurons with network behavior, a key goal of systems neuroscience.

Materials with engineered nano‐scale surface topographies, such as nanopillars, nanoneedles, and nanowires, mimic natural structures like viral spike proteins, enabling them to bypass biological barriers like the plasma membrane. These properties have led to applications in nanoelectronics for intracellular sensing and drug delivery platforms, some of which are already in clinical trials. Here, evidence is present that nanotopographic materials can induce transient openings in the nuclear membranes of various cell types without penetrating the cells, breaching the nucleo‐cytoplasmic barrier, and allowing uncontrolled molecular exchange across the nuclear membrane. These openings, induced by nanoscale curvature, are temporary and repaired through the Endosomal Sorting Complexes Required for Transport (ESCRT)‐mediated mechanisms. The findings suggest a potential for nano\topographic materials to temporarily breach the nuclear membrane with potential applications in direct nuclear sensing and delivery. [ABSTRACT FROM AUTHOR]