{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T15:35:07Z","timestamp":1776180907014,"version":"3.50.1"},"reference-count":57,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"106","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/www.science.org\/content\/page\/science-licenses-journal-article-reuse"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Robot."],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:p>Neuronal control of skeletal muscle function is ubiquitous across species for locomotion and doing work. In particular, emergent behaviors of neurons in biohybrid neuromuscular systems can advance bioinspired locomotion research. Although recent studies have demonstrated that chemical or optogenetic stimulation of neurons can control muscular actuation through the neuromuscular junction (NMJ), the correlation between neuronal activities and resulting modulation in the muscle responses is less understood, hindering the engineering of high-level functional biohybrid systems. Here, we developed NMJ-based biohybrid crawling robots with optogenetic mouse motor neurons, skeletal muscles, 3D-printed hydrogel scaffolds, and integrated onboard wireless micro\u2013light-emitting diode (\u03bcLED)\u2013based optoelectronics. We investigated the coupling of the light stimulation and neuromuscular actuation through power spectral density (PSD) analysis. We verified the modulation of the mechanical functionality of the robot depending on the frequency of the optical stimulation to the neural tissue. We demonstrated continued muscle contraction up to 20 minutes after a 1-minute-long pulsed 2-hertz optical stimulation of the neural tissue. Furthermore, the robots were shown to maintain their mechanical functionality for more than 2 weeks. This study provides insights into reliable neuronal control with optoelectronics, supporting advancements in neuronal modulation, biohybrid intelligence, and automation.<\/jats:p>","DOI":"10.1126\/scirobotics.adu5830","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T17:59:14Z","timestamp":1756922354000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Optogenetic neuromuscular actuation of a miniature electronic biohybrid robot"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4182-9993","authenticated-orcid":true,"given":"Hyegi","family":"Min","sequence":"first","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-3570","authenticated-orcid":true,"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-4476","authenticated-orcid":true,"given":"Jiaojiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Bioengineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"given":"Xiuyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL 60208, USA."},{"name":"State Key Laboratory of Mechanical System and Vibration, School of Mechanical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-6339","authenticated-orcid":true,"given":"Woong","family":"Kim","sequence":"additional","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3794-9012","authenticated-orcid":true,"given":"Onur","family":"Aydin","sequence":"additional","affiliation":[{"name":"Scott H. Fisher Multi-Cellular Engineered Living System Theme, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"given":"Sehong","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Mechanical Science and Engineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-8563","authenticated-orcid":true,"given":"Jae-Sung","family":"You","sequence":"additional","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Bioengineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Cell and Developmental Biology, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0961-117X","authenticated-orcid":true,"given":"Jongwon","family":"Lim","sequence":"additional","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Bioengineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0437-5606","authenticated-orcid":true,"given":"Katy","family":"Wolhaupter","sequence":"additional","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Bioengineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5905-8183","authenticated-orcid":true,"given":"Yikang","family":"Xu","sequence":"additional","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2315-806X","authenticated-orcid":true,"given":"Zhengguang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9113-0183","authenticated-orcid":true,"given":"Jianyu","family":"Gu","sequence":"additional","affiliation":[{"name":"Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8521-9317","authenticated-orcid":true,"given":"Xinming","family":"Li","sequence":"additional","affiliation":[{"name":"Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1068-0604","authenticated-orcid":true,"given":"Yongdeok","family":"Kim","sequence":"additional","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Materials Science and Engineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4883-1501","authenticated-orcid":true,"given":"Tarun","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4680-2968","authenticated-orcid":true,"given":"Hyun Joon","family":"Kong","sequence":"additional","affiliation":[{"name":"Scott H. Fisher Multi-Cellular Engineered Living System Theme, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Chemical and Biomolecular Engineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Chan Zuckerberg Biohub Chicago, Chicago, IL 60642, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2152-5116","authenticated-orcid":true,"given":"Taher A.","family":"Saif","sequence":"additional","affiliation":[{"name":"Scott H. Fisher Multi-Cellular Engineered Living System Theme, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Mechanical Science and Engineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0483-8359","authenticated-orcid":true,"given":"Yonggang","family":"Huang","sequence":"additional","affiliation":[{"name":"Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3830-5980","authenticated-orcid":true,"given":"John A.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA."},{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."},{"name":"Center for Bio-Integrated Electronics, Northwestern University, Evanston, IL 60208, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7225-9180","authenticated-orcid":true,"given":"Rashid","family":"Bashir","sequence":"additional","affiliation":[{"name":"Nick J. Holonyak Micro and Nanotechnology Laboratory, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Department of Bioengineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Scott H. Fisher Multi-Cellular Engineered Living System Theme, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA."},{"name":"Chan Zuckerberg Biohub Chicago, Chicago, IL 60642, USA."},{"name":"Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, Urbana, IL 61801, USA."}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.08.036"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1907051116"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abh0474"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf4292"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305371"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scirobotics.add1053"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516139113"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matt.2023.12.035"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/scirobotics.ado0051"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/scirobotics.aat4440"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401577111"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201801145"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1063\/5.0091507"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/micronano.2017.15"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat5847"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1936192100"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16883-5"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1248523"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04615-2"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1916138116"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","unstructured":"G. J. Pagan-Diaz E. Kilacarslan M. Wester S. Rahman O. Aydin L. Gapinske Y. Kim D. Buoros M. S. A. Taher R. Bashir Engineering 3D neuronal networks with directional endogenous neuronal plasticity pathways. bioRxiv 2023.05.17.540876 [Preprint] (2023). https:\/\/doi.org\/10.1101\/2023.05.17.540876.","DOI":"10.1101\/2023.05.17.540876"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404109111"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.09.001"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16985-0"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/aisy.202000237"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00835-8"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470151808.sc01h01s5"},{"key":"e_1_3_2_29_2","first-page":"3813","article-title":"Efficient differentiation of mouse embryonic stem cells into motor neurons","volume":"2012","author":"Wu C.-Y.","year":"2012","unstructured":"C.-Y. Wu, D. Whye, R. W. Mason, W. Wang, Efficient differentiation of mouse embryonic stem cells into motor neurons. J. Vis. Exp. 2012, 3813 (2012).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1501429"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.3.671"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2313590121"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.06.031"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127142"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.11.4668"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00783-3"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.8.1.62-70.1988"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.8936"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015055"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1997.0638"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03282-3"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1803875115"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15333"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.348"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-017-0324-9"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008045"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-021-00590-9"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07456"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz3267"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1420312112"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-813X(01)00066-3"},{"key":"e_1_3_2_52_2","first-page":"2451","article-title":"ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism","volume":"25","author":"Berto S.","year":"2016","unstructured":"S. Berto, N. Usui, G. Konopka, B. L. Fogel, ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism. Hum. Mol. Genet. 25, 2451\u20132464 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2018.03.004"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhv151"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.83.1.207"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05653-w"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2016.11.005"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03723-8"}],"container-title":["Science Robotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scirobotics.adu5830","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scirobotics.adu5830","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T17:59:21Z","timestamp":1756922361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scirobotics.adu5830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":57,"journal-issue":{"issue":"106","published-print":{"date-parts":[[2025,9,3]]}},"alternative-id":["10.1126\/scirobotics.adu5830"],"URL":"https:\/\/doi.org\/10.1126\/scirobotics.adu5830","relation":{},"ISSN":["2470-9476"],"issn-type":[{"value":"2470-9476","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"assertion":[{"value":"2024-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-07","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadu5830"}}