Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units
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...
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2017
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| Online Access: | http://hdl.handle.net/1721.1/107135 https://orcid.org/0000-0002-8261-2371 https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0003-4698-6488 https://orcid.org/0000-0002-7232-304X |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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 |
| author_sort | Platt, Randall Jeffrey |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:03:43Z |
| format | Article |
| id | mit-1721.1/107135 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:03:43Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1071352022-10-01T18:57:37Z Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units 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 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) Uzel, Sebastien GM Platt, Randall Jeffrey Subramanian, Vidya Pearl, Taylor M. Rowlands, Christopher Chan, Vincent Boyer, Laurie Ann So, Peter T. C. Kamm, Roger Dale 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. National Science Foundation (U.S.). Center on Emergent Behaviors of Integrated Cellular Systems (Grant CBET-0939511) National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374) Wellcome Trust-MIT Postdoctoral Fellowship Singapore. National Research Foundation Singapore-MIT Alliance in Research and Technology (SMART). BioSystems & Micromechanics IRG 2017-02-23T19:52:37Z 2017-02-23T19:52:37Z 2016-08 2015-10 Article http://purl.org/eprint/type/JournalArticle 2375-2548 http://hdl.handle.net/1721.1/107135 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. https://orcid.org/0000-0002-8261-2371 https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0003-4698-6488 https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1126/sciadv.1501429 Science Advances Creative Commons Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ application/pdf American Association for the Advancement of Science (AAAS) AAAS |
| spellingShingle | 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 Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units |
| title | Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units |
| title_full | Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units |
| title_fullStr | Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units |
| title_full_unstemmed | Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units |
| title_short | Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units |
| title_sort | microfluidic device for the formation of optically excitable three dimensional compartmentalized motor units |
| url | http://hdl.handle.net/1721.1/107135 https://orcid.org/0000-0002-8261-2371 https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0003-4698-6488 https://orcid.org/0000-0002-7232-304X |
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