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 language | English (US) |
|---|---|
| Article number | 1801521 |
| Journal | Advanced Science |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 20 2019 |
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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 journal › Article
}
TY - JOUR
T1 - Matrix Topography Regulates Synaptic Transmission at the Neuromuscular Junction
AU - Ko, Eunkyung
AU - Yu, Seung Jung
AU - Pagan-Diaz, Gelson J.
AU - Mahmassani, Ziad
AU - Boppart, Marni D.
AU - Im, Sung Gap
AU - Bashir, Rashid
AU - Kong, Hyunjoon
PY - 2019/3/20
Y1 - 2019/3/20
N2 - 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.
AB - 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.
KW - acetylcholine receptors
KW - motor neurons
KW - myotubes
KW - neural innervation
KW - neuromuscular junctions
UR - http://www.scopus.com/inward/record.url?scp=85060205547&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060205547&partnerID=8YFLogxK
U2 - 10.1002/advs.201801521
DO - 10.1002/advs.201801521
M3 - Article
AN - SCOPUS:85060205547
VL - 6
JO - Advanced Science
JF - Advanced Science
SN - 2198-3844
IS - 6
M1 - 1801521
ER -