title: Myelinating glia differentiation is regulated by extracellular matrix elasticity.
abstract: The mechanical properties of living tissues have a significant impact on cell differentiation, but remain unexplored in the context of myelin formation and repair. In the PNS, the extracellular matrix (ECM) incorporates a basal lamina significantly denser than the loosely organized CNS matrix. Inhibition of non-muscle myosin II (NMII) enhances central but impairs peripheral myelination and NMII has been implicated in cellular responses to changes in the elasticity of the ECM. To directly evaluate whether mechanotransduction plays a role in glial cell differentiation, we cultured Schwann cells (SC) and oligodendrocytes (OL) on matrices of variable elastic modulus, mimicking either their native environment or conditions found in injured tissue. We found that a rigid, lesion-like matrix inhibited branching and differentiation of OL in NMII-dependent manner. By contrast, SC developed normally in both soft and stiffer matrices. Although SC differentiation was not significantly affected by changes in matrix stiffness alone, we found that expression of Krox-20 was potentiated on rigid matrices at high laminin concentration. These findings are relevant to the design of biomaterials to promote healing and regeneration in both CNS and PNS, via transplantation of glial progenitors or the implantation of tissue scaffolds.
authors.affiliation: Hunter College, Department of Biological Sciences, New York, NY 10065, USA.|The Graduate Center, Molecular Cellular and Developmental Biology, The City University of New York, NY 10016, USA.
authors.forename: Mateusz M
authors.initials: MM
authors.lastname: Urbanski
authors.affiliation: Hunter College, Department of Biological Sciences, New York, NY 10065, USA.
authors.forename: Lyle
authors.initials: L
authors.lastname: Kingsbury
authors.affiliation: Hunter College, Department of Biological Sciences, New York, NY 10065, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moussouros
authors.affiliation: Hunter College, Department of Biological Sciences, New York, NY 10065, USA.
authors.forename: Imran
authors.initials: I
authors.lastname: Kassim
authors.affiliation: Hunter College, Department of Biological Sciences, New York, NY 10065, USA.
authors.forename: Saraf
authors.initials: S
authors.lastname: Mehjabeen
authors.affiliation: Molecular Cytology Core Facility, Zuckerman Research Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Navid
authors.initials: N
authors.lastname: Paknejad
authors.affiliation: Hunter College, Department of Biological Sciences, New York, NY 10065, USA.|The Graduate Center, Molecular Cellular and Developmental Biology, The City University of New York, NY 10016, USA.
authors.forename: Carmen V
authors.initials: CV
authors.lastname: Melendez-Vasquez
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D051381:Rats