A high-throughput spheroid fusion platform for the templated-assembly of 3D neuromuscular junctions

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Neurons help control movement by sending conveying electrical impulses from the brain and spinal cord to the muscles. The connection between the neurons and muscles happens in the human body at specific places called neuromuscular junctions (NMJ). Understanding the interactions between neurons and muscle cells is crucial to understand neuromuscular development and dysfunction. At the moment, there are no available human three-dimensional models that can be used to study this junction, hence animal models are routinely used instead. However, animal NMJ differs significantly from the human ones. Hence, it is critical to develop accurate human models of the NMJ. In the past few years, our team has developed novel technologies that permit the formation of lab-grown tissue that can be used to recapitulate human physiology.In this project, we will create a novel in-vitro model neuromuscular junction to alleviate the need for animal models. We will grow both neurons and muscle cells into three dimensional cultures and force them to assemble using networks of microtraps. We will generate for the first time truly 3D organoids with hundreds of such junctions per experiment, a number at least one order of magnitude higher than previous attempts. The junctions will be validated by measuring muscle contraction upon chemical stimulation of the neurons. This will ensure that the models we create have the highest relevance to human physiology and can be used as a platform for future biomedical research.