Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons.
Myelination is a key biological process wherein glial cells such as oligodendrocytes wrap myelin around neuronal axons, forming an insulative sheath that accelerates signal propagation down the axon. A major obstacle to understanding myelination is the challenge of visualizing and reproducibly quant...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0290521 |
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| author | Mingyu Yang Calliope J L Martin Kavin Kowsari Anna Jagielska Krystyn J Van Vliet |
| author_facet | Mingyu Yang Calliope J L Martin Kavin Kowsari Anna Jagielska Krystyn J Van Vliet |
| author_sort | Mingyu Yang |
| collection | DOAJ |
| description | Myelination is a key biological process wherein glial cells such as oligodendrocytes wrap myelin around neuronal axons, forming an insulative sheath that accelerates signal propagation down the axon. A major obstacle to understanding myelination is the challenge of visualizing and reproducibly quantifying this inherently three-dimensional process in vitro. To this end, we previously developed artificial axons (AAs), a biocompatible platform consisting of 3D-printed hydrogel-based axon mimics designed to more closely recapitulate the micrometer-scale diameter and sub-kilopascal mechanical stiffness of biological axons. First, we present our platform for fabricating AAs with tunable axon diameter, stiffness, and inter-axonal spacing. Second, we demonstrate that increasing the Young's modulus E or stiffness of polymer comprising the AAs increases the extent of myelin ensheathment by rat oligodendrocytes. Third, we demonstrate that the responses of oligodendrocytes to pro-myelinating compounds are also dependent on axon stiffness, which can affect compounds efficacy and the relative ranking. These results reinforce the importance of studying myelination in mechanically representative environments, and highlight the importance of considering biophysical cues when conducting drug screening studies. |
| format | Article |
| id | doaj-art-b4134c229fee4d8bb9f0a6deae85d39f |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-b4134c229fee4d8bb9f0a6deae85d39f2025-02-05T05:32:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e029052110.1371/journal.pone.0290521Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons.Mingyu YangCalliope J L MartinKavin KowsariAnna JagielskaKrystyn J Van VlietMyelination is a key biological process wherein glial cells such as oligodendrocytes wrap myelin around neuronal axons, forming an insulative sheath that accelerates signal propagation down the axon. A major obstacle to understanding myelination is the challenge of visualizing and reproducibly quantifying this inherently three-dimensional process in vitro. To this end, we previously developed artificial axons (AAs), a biocompatible platform consisting of 3D-printed hydrogel-based axon mimics designed to more closely recapitulate the micrometer-scale diameter and sub-kilopascal mechanical stiffness of biological axons. First, we present our platform for fabricating AAs with tunable axon diameter, stiffness, and inter-axonal spacing. Second, we demonstrate that increasing the Young's modulus E or stiffness of polymer comprising the AAs increases the extent of myelin ensheathment by rat oligodendrocytes. Third, we demonstrate that the responses of oligodendrocytes to pro-myelinating compounds are also dependent on axon stiffness, which can affect compounds efficacy and the relative ranking. These results reinforce the importance of studying myelination in mechanically representative environments, and highlight the importance of considering biophysical cues when conducting drug screening studies.https://doi.org/10.1371/journal.pone.0290521 |
| spellingShingle | Mingyu Yang Calliope J L Martin Kavin Kowsari Anna Jagielska Krystyn J Van Vliet Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons. PLoS ONE |
| title | Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons. |
| title_full | Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons. |
| title_fullStr | Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons. |
| title_full_unstemmed | Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons. |
| title_short | Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons. |
| title_sort | myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons |
| url | https://doi.org/10.1371/journal.pone.0290521 |
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