Abstract
The neural stem cell (NSC) niche is a highly vascularized microenvironment that supplies stem cells with relevant biological and chemical cues. However, the NSCs’ proximity to the vasculature also means that the NSCs are subjected to permanent tissue deformation effected by the vessels’ heartbeat-induced pulsatile movements. Cultivating NSCs under common culture conditions neglects the—yet unknown—influence of this cyclic mechanical strain on neural stem cells. Under the hypothesis that pulsatile strain should affect essential NSC functions, a cyclic uniaxial strain was applied under biomimetic conditions using an in-house developed stretching system based on cross-linked polydimethylsiloxane (PDMS) elastomer. While lineage commitment remained unaffected by cyclic deformation, strain affected NSC quiescence and cytoskeletal organization. Unexpectedly, cyclically stretched stem cells aligned in stretch direction, a phenomenon unknown for other types of cells in the mammalian organism. The same effect was observed for young astrocytes differentiating from NSCs. In contrast, young neurons differentiating from NSCs did not show mechanoresponsiveness. The exceptional orientation of NSCs and young astrocytes in the stretch direction was blocked upon RhoA activation and went along with a lack of stress fibers. Compared to postnatal astrocytes and mature neurons, NSCs and their young progeny displayed characteristic and distinct mechanoresponsiveness. Data suggest a protective role of young astrocytes in mixed cultures of differentiating neurons and astrocytes by mitigating the mechanical stress of pulsatile strain on developing neurons.
Highlights
Neural stem cells (NSC) are the source of all neurons and glial cells in the central nervous system
Due to the high cellular dynamics of migrating cells such as neural stem cell (NSC), we questioned the extent to which cyclic substrate strain will deform NSCs that are growing on top of the elastomers
To examine the immediate response to cyclic strain, NSCs were subjected to mechanical deformation while being observed via live-cell microscopy
Summary
Neural stem cells (NSC) are the source of all neurons and glial cells in the central nervous system. NSCs sense chemical and mechanical cues located in their specialized extracellular environment, referred to as the neural stem cell niche. In this specialized microenvironment, NSCs and progenitor cells are supplied by numerous extracellular signals that regulate stem cell characteristics (for review see Miller and GauthierFisher, 2009). Another study reported a change of the substrate’s physical property, i.e., conductivity, after stretch as a cue to tune stem cell lineage commitment to promote neuronal differentiation (Srivastava et al, 2013)
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