A customizable microfluidic platform for medium-throughput modeling of neuromuscular circuits

Neuromuscular circuits (NMCs) are vital for voluntary movement, and effective models of NMCs are needed to understand the pathogenesis of, as well as to identify effective treatments for, multiple diseases, including Duchenne's muscular dystrophy and amyotrophic lateral sclerosis. Microfluidics...

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Bibliographic Details
Published in:	Biomaterials Vol. 225; p. 119537
Main Authors:	Bellmann, Jessica, Goswami, Ruchi Y., Girardo, Salvatore, Rein, Nelly, Hosseinzadeh, Zohreh, Hicks, Michael R., Busskamp, Volker, Pyle, April D., Werner, Carsten, Sterneckert, Jared
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-12-2019
Subjects:	Cell Adhesion - drug effects Cell Differentiation - drug effects Cells, Cultured Dimethylpolysiloxanes - chemistry Humans Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - drug effects Laminin - pharmacology Maleates - chemistry Microfluidics Microfluidics - methods Motor Neurons - cytology Motor Neurons - drug effects Motor unit Muscle Fibers, Skeletal - cytology Muscle Fibers, Skeletal - drug effects Neuromuscular circuit Neuromuscular Junction - physiology Peptides - pharmacology Plasma Gases - chemistry poly(ethylene-alt-maleic anhydride) Polyethylenes - chemistry Rabies viral tracing Skeletal muscle poly(ethylene-alt-maleic anhydride) Rabies viral tracing Microfluidics Skeletal muscle Motor unit Neuromuscular circuit
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Summary:	Neuromuscular circuits (NMCs) are vital for voluntary movement, and effective models of NMCs are needed to understand the pathogenesis of, as well as to identify effective treatments for, multiple diseases, including Duchenne's muscular dystrophy and amyotrophic lateral sclerosis. Microfluidics are ideal for recapitulating the central and peripheral compartments of NMCs, but myotubes often detach before functional NMCs are formed. In addition, microfluidic systems are often limited to a single experimental unit, which significantly limits their application in disease modeling and drug discovery. Here, we developed a microfluidic platform (MFP) containing over 100 experimental units, making it suitable for medium-throughput applications. To overcome detachment, we incorporated a reactive polymer surface allowing customization of the environment to culture different cell types. Using this approach, we identified conditions that enable long-term co-culture of human motor neurons and myotubes differentiated from human induced pluripotent stem cells inside our MFP. Optogenetics demonstrated the formation of functional NMCs. Furthermore, we developed a novel application of the rabies tracing assay to efficiently identify NMCs in our MFP. Therefore, our MFP enables large-scale generation and quantification of functional NMCs for disease modeling and pharmacological drug targeting. •Manufacture of a microfluidic platform (MFP) for medium-throughput applications.•Silanization and plasma treatment enables incorporation of PEMA film into MFP.•PEMA based coatings enable culture of iPSC-derived neurons and myotubes in MFPs.•RABV tracing and optogenetics showed neuromuscular circuit formation in MFPs.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 JB, SG, ADP, CW, and JS conceptualized and administered the project. JB, and RYG investigated and acquired experimental data. JB, MRH, NR, ADP, ZH and CW developed experimental protocols and contributed reagents and analysis. JB, RYG, SG and JS wrote the manuscript. All authors revised and proof-read the manuscript. Author contributions
ISSN:	0142-9612 1878-5905
DOI:	10.1016/j.biomaterials.2019.119537