Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units
Name
Boyer_Microfluidic device.pdf
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6.65 MB
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Checksum (MD5)
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Author(s)
Platt, Randall Jeffrey
Subramanian, Vidya
Pearl, Taylor M.
Rowlands, Christopher
Chan, Vincent
Boyer, Laurie Ann
So, Peter T. C.
Kamm, Roger Dale
Uzel, Sebastien Guy Marcel
Date Issued
August 2016
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Uzel, S. G. M. et al. “Microfluidic Device for the Formation of Optically Excitable, Three-Dimensional, Compartmentalized Motor Units.” Science Advances 2.8 (2016): e1501429–e1501429.
Version
Final published version
Abstract
Motor units are the fundamental elements responsible for muscle movement. They are formed by lower motor neurons and their muscle targets, synapsed via neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders (such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result of traumatic injuries affects millions of lives each year. Developing in vitro assays that closely recapitulate the physiology of neuromuscular tissues is crucial to understand the formation and maturation of NMJs, as well as to help unravel the mechanisms leading to their degeneration and repair. We present a microfluidic platform designed to coculture myoblast-derived muscle strips and motor neurons differentiated from mouse embryonic stem cells (ESCs) within a three-dimensional (3D) hydrogel. The device geometry mimics the spinal cord–limb physical separation by compartmentalizing the two cell types, which also facilitates the observation of 3D neurite outgrowth and remote muscle innervation. Moreover, the use of compliant pillars as anchors for muscle strips provides a quantitative functional readout of force generation. Finally, photosensitizing the ESC provides a pool of source cells that can be differentiated into optically excitable motor neurons, allowing for spatiodynamic, versatile, and noninvasive in vitro control of the motor units.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Mechanical Engineering
Singapore-MIT Alliance in Research and Technology (SMART)
Terms of Use
Creative Commons Attribution-NonCommercial 4.0 International
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/sciadv.1501429
