Abstract

Recreation of a muscle that can be controlled by the nervous system would provide a major breakthrough for treatments of injury and diseases. However, the underlying basis of how neuron–muscle 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-talk 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.

Original languageEnglish (US)
Article number1801521
JournalAdvanced Science
Volume6
Issue number6
DOIs
StatePublished - Mar 20 2019

Fingerprint

Neuromuscular Junction
Skeletal Muscle Fibers
Synaptic Transmission
Topography
topography
muscles
Substrates
Muscle
matrices
stem cells
curare
Stem cells
neurons
grooves
Neurons
Neural Stem Cells
recreation
acetylcholine
Curare
Muscles

Keywords

  • acetylcholine receptors
  • motor neurons
  • myotubes
  • neural innervation
  • neuromuscular junctions

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Matrix Topography Regulates Synaptic Transmission at the Neuromuscular Junction. / Ko, Eunkyung; Yu, Seung Jung; Pagan-Diaz, Gelson J.; Mahmassani, Ziad; Boppart, Marni D.; Im, Sung Gap; Bashir, Rashid; Kong, Hyunjoon.

In: Advanced Science, Vol. 6, No. 6, 1801521, 20.03.2019.

Research output: Contribution to journalArticle

Ko, Eunkyung ; Yu, Seung Jung ; Pagan-Diaz, Gelson J. ; Mahmassani, Ziad ; Boppart, Marni D. ; Im, Sung Gap ; Bashir, Rashid ; Kong, Hyunjoon. / Matrix Topography Regulates Synaptic Transmission at the Neuromuscular Junction. In: Advanced Science. 2019 ; Vol. 6, No. 6.
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