Static stretch affects neural stem cell differentiation in an extracellular matrix-dependent manner

Abstract

Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice. Other types of mechanical stimuli, such as stretch (tensile strain), occur during CNS development and trauma, but their consequences for NSPC differentiation have not been reported. We delivered a 10% static equibiaxial stretch to NSPCs and examined effects on differentiation. We found static stretch specifically impacts NSPC differentiation into oligodendrocytes, but not neurons or astrocytes, and this effect is dependent on particular extracellular matrix (ECM)-integrin linkages. Generation of oligodendrocytes from NSPCs was reduced on laminin, an outcome likely mediated by the α6 laminin-binding integrin, whereas similar effects were not observed for NSPCs on fibronectin. Our data demonstrate a direct role for tensile strain in dictating the lineage choice of NSPCs and indicate the dependence of this phenomenon on specific substrate materials, which should be taken into account for the design of biomaterials for NSPC transplantation.

β1 integrin signaling in asymmetric migration of keratinocytes under mechanical stretch in a co-cultured wound repair model

“…Here an important issue is why and how the static stretch, rather than the cyclic stretch, affects the cell migration. A cell is able to sense the deformation of elastic membrane initially and to reach the steady phase under a static stretch [39]. This interprets well why the early phase up-regulation was observed for the expressions of β1 integrin and vinculin within the first hour of stretch onset (Fig.…”

Epigenetic control of oligodendrocyte development: adding new players to old keepers

“…Other sources of extracellular signals, such as spatial constraints and the stiffness of the extracellular matrix, have recently been shown to directly modulate OPC migration, proliferation, and differentiation [37-40]. For example, plating OPCs at a high density promotes their differentiation, an effect that mainly depends on spatial constraints rather than intercellular interactions, as culturing progenitors at a normal density with inert microspheres also promotes myelination [40].…”

Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

“…Mechanical stretching is also an important regulatory cue for NSCs, as they encounter a plethora of active forces during tissue morphogenesis and due to cyclic deformation of vasculature by blood flow. Arulmoli et al recently found that a 10% static equibiaxial strain significantly reduced oligodendrocyte fate commitment (Figure 1A, B), whereas neurogenesis and astrogenesis were unaffected [40], representing the first report that static stretch can impact NSC behavior in vitro. Importantly, the authors included a “prestretched” condition in which cells were seeded after substrate stretching to distinguish between the effects of the stretch stimulus and the ~100-fold increase in stiffness induced by the stretch (1.6 MPa vs 10 kPa).…”