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

Abstract

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.

Stimulus‐Responsive Amino Acids Behind In Situ Assembled Bioactive Peptide Materials

“…The mechanistic studies revealed that the enhanced cellular proliferation is attributed to the conventional Hippo mechanotransduction pathway involving translocation of unphosphorylated YAP protein into cell nuclear, which subsequently activated the downstream proliferation‐related genes. Simultaneously, we also found the photo‐regulated molecular movement in mechanical hydrogels affected the differentiation of embryonic stem cells [133] . This kind mechanically dynamic hydrogels are the first examples of artificial extracellular matrices able to actively stimulate cells by intrinsic mechanical cue, thus providing a unique strategy for regulating cell fate through materials engineering.…”

“…Simultaneously, we also found the photo-regulated molecular movement in mechanical hydrogels affected the differentiation of embryonic stem cells. [133] This kind mechanically dynamic hydrogels are the first examples of artificial extracellular matrices able to actively stimulate cells by intrinsic mechanical cue, thus providing a unique strategy for regulating cell fate through materials engineering.…”