Biomimicking fiber platform with tunable stiffness to study mechanotransduction reveals stiffness enhances oligodendrocyte differentiation but impedes myelination through YAP-dependent regulation

Ong, William, Marinval, Nicolas, Lin, Junquan, Nai, Mui Hoon, Chong, Yee Song, Pinese, Coline, Sajikumar, Sreedharan, Lim, Chwee Teck, ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377, Bechler, Marie E. and Chew, Sing Yian (2020) Biomimicking fiber platform with tunable stiffness to study mechanotransduction reveals stiffness enhances oligodendrocyte differentiation but impedes myelination through YAP-dependent regulation. Small, 16 (37). ISSN 1613-6810

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Abstract

A key hallmark of many diseases, especially those in the central nervous system (CNS), is the change in tissue stiffness due to inflammation and scarring. However, how such changes in microenvironment affect the regenerative process remains poorly understood. Here, a biomimicking fiber platform that provides independent variation of fiber structural and intrinsic stiffness is reported. To demonstrate the functionality of these constructs as a mechanotransduction study platform, these substrates are utilized as artificial axons and the effects of axon structural versus intrinsic stiffness on CNS myelination are independently analyzed. While studies have shown that substrate stiffness affects oligodendrocyte differentiation, the effects of mechanical stiffness on the final functional state of oligodendrocyte (i.e., myelination) has not been shown prior to this. Here, it is demonstrated that a stiff mechanical microenvironment impedes oligodendrocyte myelination, independently and distinctively from oligodendrocyte differentiation. Yes-associated protein is identified to be involved in influencing oligodendrocyte myelination through mechanotransduction. The opposing effects on oligodendrocyte differentiation and myelination provide important implications for current work screening for promyelinating drugs, since these efforts have focused mainly on promoting oligodendrocyte differentiation. Thus, the platform may have considerable utility as part of a drug discovery program in identifying molecules that promote both differentiation and myelination.

Item Type: Article
Additional Information: Funding Information: This work was supported partially by the Singapore National Research Foundation under its NMRC-CBRG grant (NMRC/CBRG/0096/2015), administered by the Singapore Ministry of Health's National Medical Research Council, and also by the MOE Tier 1 grant (RG38/19). The NTU Research Scholarship supporting W.O. and J.L. is also acknowledged. Funding Information: This work was supported partially by the Singapore National Research Foundation under its NMRC‐CBRG grant (NMRC/CBRG/0096/2015), administered by the Singapore Ministry of Health's National Medical Research Council, and also by the MOE Tier 1 grant (RG38/19). The NTU Research Scholarship supporting W.O. and J.L. is also acknowledged.
Uncontrolled Keywords: biomaterials,mechanotransduction,myelination,neural tissue engineering,tunable stiffness platforms,biotechnology,biomaterials,chemistry(all),materials science(all) ,/dk/atira/pure/subjectarea/asjc/1300/1305
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 19 Jul 2022 13:30
Last Modified: 21 Jul 2022 10:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/86611
DOI: 10.1002/smll.202003656

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