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Yet, these technologies often require genetic or structural alterations of neurons, disrupting their natural activity. Here, we introduce the Graphene-Mediated Optical Stimulation (GraMOS) platform, which leverages graphene\u2019s optoelectronic properties and its ability to efficiently convert light into electricity. Using GraMOS in longitudinal studies, we found that repeated optical stimulation enhances the maturation of hiPSC-derived neurons and brain organoids, underscoring GraMOS\u2019s potential for regenerative medicine and neurodevelopmental studies. To explore its potential for disease modeling, we applied short-term GraMOS to Alzheimer\u2019s stem cell models, uncovering disease-associated alterations in neuronal activity. Finally, we demonstrated a proof-of-concept for neuroengineering applications by directing robotic movements with GraMOS-triggered signals from graphene-interfaced brain organoids. By enabling precise, non-invasive neural control across timescales from milliseconds to months, GraMOS opens new avenues in neurodevelopment, disease treatment, and robotics.<\/jats:p>","DOI":"10.1038\/s41467-025-62637-6","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T09:02:14Z","timestamp":1755680534000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Non-genetic neuromodulation with graphene optoelectronic actuators for disease models, stem cell maturation, and biohybrid robotics"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8117-8174","authenticated-orcid":false,"given":"Elena","family":"Molokanova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6760-9190","authenticated-orcid":false,"given":"Teng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4948-3922","authenticated-orcid":false,"given":"Pragna","family":"Vasupal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0877-5081","authenticated-orcid":false,"given":"Volodymyr P.","family":"Cherkas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4057-2348","authenticated-orcid":false,"given":"Prashant","family":"Narute","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana S. 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E.M. is the inventor and applicant on patents (US10137150B2, US10688127B2, CN106458601B, JP6635383B2, EP3157866B1) related to the graphene-based optical stimulation technology, and its applications, including its use for driving activity-dependent maturation of stem cell-derived cells. A.R.M is a co-founder and has an equity interest in TISMOO, a company dedicated to genetic analysis and brain organoid modeling focusing on therapeutic applications customized for autism spectrum disorder and other neurological disorders with genetic origins. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. E.M., A.S., and A.R.M. declare no other competing interests. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study does not involve experiment involving animals, human participants, or clinical samples. All research presented in this manuscript was conducted in accordance with ethical guidelines and best practices for scientific integrity and responsible collaboration. No part of the study involved research in resource-limited settings or populations from low- or middle-income countries. All contributors to this work were properly credited for their efforts and intellectual input.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Inclusion & Ethics Statement"}}],"article-number":"7499"}}