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.

由细胞内过程或外力来源引起的干细胞生态位中的机械提示会显着影响干细胞的基本功能，例如自我更新和分化。表现出由机械运动产生的固有机械提示的人工细胞基质的创造仍然很少。在本文中，我们报道了发生光诱导的定向域滑动运动的机械动态水凝胶基质及其在调节胚胎干细胞（ESC）分化中的作用。通过具有光笼罩的半胱氨酸残基的亲水性和疏水性交替肽的自组装来制备机械动力水凝胶。在光照射下 笼状肽的组装被转化为未平衡的非笼状肽双层，该双层经历了由热力学上有利的疏水性塌陷转变引起的定向域滑动。在机械动力水凝胶上培养鼠类胚胎干细胞会导致向外胚层谱系的分化分化。我们进一步表明，机械动力水凝胶刺激了机械转导蛋白Yes-associated蛋白（YAP）易位进入细胞核，暗示了潜在的机械转导机制导致ESCs的分化分化。由机械动力水凝胶引起的ESC的外胚层分化偏见的发现暗示了机械动力水凝胶作为用于疾病治疗和组织再生的生物材料的巨大潜力。