Photoinduced directional domain sliding motion in peptide hydrogels promotes ectodermal differentiation of embryonic stem cells

Mechanical cues present in the stem cell niche resulting from intracellular processes or external force sources significantly affect the basic functions of stem cells such as self-renewal and differentiation. Creation of artificial cellular matrices exhibiting intrinsic mechanical cues generated by mechanical movements remains scarce. Herein, we reported on mechanically dynamic hydrogel matrices undergoing photo-induced directional domain sliding movement and their role in regulating embryonic stem cell (ESC) differentiation. The mechanically dynamic hydrogels were prepared via the self-assembly of an alternating hydrophilic and hydrophobic peptide with a photocaged cysteine residue. Upon light irradiation, the assemblies of the caged peptide were converted to non-equilibrated non-caged peptide bilayers that underwent the directional domain sliding motion induced by the thermodynamically favorable hydrophobic collapse transition. Culturing murine ESCs on the mechanically dynamic hydrogels resulted in biased differentiation toward the ectodermal lineage. We further showed that the mechanically dynamic hydrogels stimulated the translocation of a mechanotransduction protein Yes-associated protein (YAP) into the nucleus, implicating a potential mechanotransduction mechanism for the biased differentiation of ESCs. The finding of the biased ectodermal differentiation of ESCs induced by the mechanically dynamic hydrogels implies the great potency of the mechanically dynamic hydrogels as biomaterials for disease therapy and tissue regeneration in the future.