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

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Motor neurons connect the CNS to muscle, yet the development and homeostasis ofthese synaptic connection is difficult to study in vitro, because contractile myofibersare unstable in standard culture systems. We propose to develop a human iPSCneuromuscularcircuit model, in which synthetic elastomer nanofibers support longtermstability, alignment and contraction of myofibers, innervated by motor neurons in96-well plates. Optogenetic stimulation of motor neurons will elicit myofibercontractions, providing a functional readout of neuromuscular transmission. Highcontentimaging is used to quantify axons, myofibers, and neuromuscular synapses.The model will be tested with circuits carrying mutations that affect nerve-muscleconnectivity.