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However, the underlying basis of how neuron\u2013muscle interfaces are formed is still not understood sufficiently. Here, it is hypothesized that substrate topography regulates neural innervation and synaptic transmission by mediating the cross\u2010talk between neurons and muscles. This hypothesis is examined by differentiating neural stem cells on the myotubes, formed on the substrate with controlled groove width. The substrate with the groove width of 1600 nm, a similar size to the myofibril diameter, serves to produce larger and aligned myotubes than the flat substrate. The myotubes formed on the grooved substrate display increases in the acetylcholine receptor expression. Reciprocally, motor neuron progenitor cells differentiated from neural stem cells innervate the larger and aligned myotubes more actively than randomly oriented myotubes. As a consequence, mature and aligned myotubes respond to glutamate (i.e., an excitatory neurotransmitter) and curare (i.e., a neuromuscular antagonist) more rapidly and homogeneously than randomly oriented myotubes. The results of this study will be broadly useful for improving the quality of engineered muscle used in a series of applications including drug screening, regeneration therapies, and biological machinery assembly.<\/jats:p>","DOI":"10.1002\/advs.201801521","type":"journal-article","created":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T00:19:39Z","timestamp":1547770779000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Matrix Topography Regulates Synaptic Transmission at the Neuromuscular Junction"],"prefix":"10.1002","volume":"6","author":[{"given":"Eunkyung","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Illinois at Urbana\u2013Champaign  Urbana IL 61801 USA"},{"name":"Department of Bioengineering Micro and Nanotechnology Laboratory University of Illinois at Urbana\u2013Champaign  Urbana IL 61801 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Jung","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering and KI for the Nano Century Korea Advanced Institute of Science and Technology (KAIST)  Daejeon 305\u2010701 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gelson J.","family":"Pagan\u2010Diaz","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Micro and Nanotechnology Laboratory University of Illinois at Urbana\u2013Champaign  Urbana IL 61801 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad","family":"Mahmassani","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Community Health Beckman Institute for Advanced Science and Technology University of Illinois at Urbana\u2013Champaign  Urbana IL 61801 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marni D.","family":"Boppart","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Community Health Beckman Institute for Advanced Science and Technology University of Illinois at Urbana\u2013Champaign  Urbana IL 61801 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Gap","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering and KI for the Nano Century Korea Advanced Institute of Science and Technology (KAIST)  Daejeon 305\u2010701 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Bashir","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Micro and Nanotechnology Laboratory University of Illinois at Urbana\u2013Champaign  Urbana IL 61801 USA"},{"name":"Carl R. 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