A Multi-Well Human iPSC Neuromuscular Disease Model on Elastomer Nanofibers

Motor neurons connect the CNS to muscle, yet the development and homeostasis of
these synaptic connection is difficult to study in vitro, because contractile myofibers
are unstable in standard culture systems. We propose to develop a human iPSCneuromuscular
circuit model, in which synthetic elastomer nanofibers support longterm
stability, alignment and contraction of myofibers, innervated by motor neurons in
96-well plates. Optogenetic stimulation of motor neurons will elicit myofiber
contractions, providing a functional readout of neuromuscular transmission. Highcontent
imaging is used to quantify axons, myofibers, and neuromuscular synapses.
The model will be tested with circuits carrying mutations that affect nerve-muscle
connectivity.