Lower fluidity of supported lipid bilayers promotes neuronal differentiation of neural stem cells by enhancing focal adhesion formation.

Extensive studies have been performed to understand how the mechanical properties of a stem cell's microenvironment influence its behaviors. Supported lipid bilayers (SLBs), a well-known biomimetic platform, have been used to mimic the dynamic characteristics of the extracellular matrix (ECM) because of their fluidity. However, the effect of the fluidity of SLBs on stem cell fate is unknown. We constructed SLBs with different fluidities to explore the influence of fluidity on the differentiation of neural stem cells (NSCs). The results showed that the behavior of NSCs was highly dependent on the fluidity of SLBs. Low fluidity resulted in enhanced focal adhesion formation, a dense network of stress fibers, stretched and elongated cellular morphology and increased neuronal differentiation, while high fluidity led to less focal adhesion formation, immature stress fibers, round cellular morphology and more astrocyte differentiation. Mechanistic studies revealed that low fluidity may have enhanced focal adhesion formation, which activated FAK-MEK/ERK signaling pathways and ultimately promoted neuronal differentiation of NSCs. This work provides a strategy for manipulating the dynamic matrix surface for the development of culture substrates and tissue-engineered scaffolds, which may aid the understanding of how the dynamic ECM influences stem cell behaviors as well as improve the efficacy of stem cell applications.