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

William Ong, Nicolas Marinval, Junquan Lin, Mui Hoon Nai, Yee Song Chong, Coline Pinese, Sreedharan Sajikumar, Chwee Teck Lim, Charles ffrench-Constant, Marie E. Bechler, Sing Yian Chew

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Article number2003656
JournalSmall
Volume16
Issue number37
Early online date12 Aug 2020
DOIs
Publication statusPublished - 17 Sep 2020

Keywords

  • biomaterials
  • mechanotransduction
  • myelination
  • neural tissue engineering
  • tunable stiffness platforms

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