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Generation of Human Motor Units with Functional Neuromuscular Junctions in Microfluidic Devices
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Mechanically patterned neuromuscular junctions-in-a-dish have improved functional maturation.

Cassandra L Happe1, Kevin P Tenerelli1, Anastasia K Gromova2

  • 1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093.

Molecular Biology of the Cell
|May 13, 2017
PubMed
Summary

Mechanically patterned substrates improve neuromuscular junction (NMJ) models by guiding myoblast alignment and differentiation. This creates more functional NMJ-in-a-dish models for studying motor neuron diseases and drug discovery.

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Area of Science:

  • Biomedical Engineering
  • Neuroscience
  • Cell Biology

Background:

  • Motor neuron (MN) diseases involve neuromuscular junction (NMJ) degeneration.
  • Current NMJ-in-a-dish models exhibit immature synapses and asynchronous contractions.

Purpose of the Study:

  • To develop improved NMJ-in-a-dish models using mechanically patterned substrates.
  • To enhance myotube maturation, NMJ formation, and functional activity.

Main Methods:

  • Utilized mechanically patterned (MP) extracellular matrices with alternating soft and stiff stripes.
  • Investigated myoblast durotaxis, alignment, differentiation, fusion, and NMJ formation.
  • Assessed acetylcholine (ACh) receptor clusters, MuSK and Lrp4 expression, and muscle contraction.

Main Results:

  • MP substrates induced myoblast alignment, differentiation, and fusion into patterned myotubes.
  • MP substrates supported larger ACh receptor clusters and increased MuSK/Lrp4 expression.
  • MP substrates facilitated robust, mature muscle-like contractions and enhanced NMJ formation with MNs.

Conclusions:

  • MP matrices generate more functionally active NMJs-in-a-dish.
  • These improved models can advance the study of motor neuron diseases and drug discovery.