Mechanical regulation of oligodendrocyte biology

Mechanosensitivity of Human Oligodendrocytes

“…Cells were grown for an additional 8 days (day 68) in maturation medium, and oligodendrocytes were stained with the O4 antibody (pink). (B) Range of stiffness (Young’s modulus) reported for brain tissue and typical oligodendrocyte cell culture substrata in the literature (Makhija et al, 2020 ). (C) PAAm hydrogels were prepared to span the range of physiological and pathological brain stiffness previously probed with rat primary oligodendrocytes (Jagielska et al, 2012 ).…”

“…The mechanosensitivity of oligodendrocytes may have important implications in CNS pathology, and for the development of drug and cell-based therapies for remyelination. These and other implications were reviewed recently (Makhija et al, 2020).…”

“…These cells reside in dynamic and complex microenvironments. The physical properties and forces in this “niche” provide cues that can regulate behavior and cell fate (Makhija et al, 2020 ). Changes in this mechanical landscape are characteristic of developmental (Franze, 2013 ; Budday et al, 2015 ) and aging (Morawski et al, 2014 ) processes, as well as various CNS disorders that include multiple sclerosis (MS; Streitberger et al, 2012 ; Urbanski et al, 2019 ), Alzheimer’s (Murphy et al, 2011 , 2016 ) and Parkinson’s (Lipp et al, 2013 ).…”

“…Engagement of the actomyosin cytoskeletal network spans the cytoplasm and facilitates the transmission of force or displacement to the nuclear membrane through signaling cascades (Ingber, 2006 ). In the CNS, mechanical changes and dysregulation of mechanotransduction are signatures of neurological disorders (Makhija et al, 2020 ) that can correlate with behavioral dysfunction (Wang et al, 2018 ). Given the direct role of oligodendrocytes in myelination and neuronal health, we and others seek improved understanding of how these glial cells may respond to mechanical and other cues that limit or promote repair in demyelinating diseases such as MS.…”

“…Oligodendrocytes respond to both time-invariant (static) and time-varying (dynamic) mechanical cues. This mechanosensitivity has been established in the last decade using in vitro murine models almost exclusively, due to the practical limitations of obtaining glial cells from human CNS tissue (recently reviewed by Makhija et al, 2020 ). Oligodendrocyte progenitor cell (OPC) proliferation, migration, differentiation, and maturation respond to the mechanical stiffness of the materials to which these cells adhere (Jagielska et al, 2012 ; Lourenço et al, 2016 ; Urbanski et al, 2016 ; Segel et al, 2019 ), to applied uniaxial and biaxial strain (Hernandez et al, 2016 ; Jagielska et al, 2017 ), and to physical constraints (Rosenberg et al, 2008 ; Lee et al, 2013 ; Diao et al, 2015 ).…”