Figure 2.

Signaling pathways generically involved in mechanotransduction and proposed model for the influence of biophysical elements during OL differentiation. (A) Integrins (heterodimeric transmembrane receptors composed by α and β subunits) engage ECM proteins (Wang et al., 1993) on the extracellular region, in turn recruiting intracellular adaptor proteins that subsequently bind to actin cytoskeleton. Upon integrin activation, several focal adhesion proteins (SFKs, Focal Adhesion Kinase (FAK), Talin) are recruited and activated, promoting cytoskeleton and cellular dynamics (Huveneers and Danen, 2009). On stiffer platforms, focal adhesions (FAs) are reinforced, inducing further activation of RhoA, ROCK and myosin-II, and consequently, cytoskeleton tension increases (left panel). On softer substrates, cytoskeleton tension is lower, due to reduced maturation of FAs and lower activation of RhoA, ROCK and myosin-II (right panel). (B) The model presented proposes that inactivation of RhoA caused by activation of Fyn in response to engagement of α6β1 integrin by laminin-2 (Colognato et al., 2004; Bechler et al., 2015) combined with soft substrates contributes to low actomyosin contractility, favoring OL differentiation (left panel). Engagement of αvβ3 integrin by fibronectin leads to activation of Lyn (Colognato et al., 2004), promoting maintenance of OPCs, which also seems to be favored by soft substrates (right panel). Please refer to the main text for further details.