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

含光诱导片段定向滑动多肽水凝胶诱导胚胎干细胞的外胚层分化

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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.

摘要

由细胞内行为或外源力引起的干细胞龛中存在的机械信号对干细胞的自我恢复和分化等基本功能具有重要影响. 然而, 关于具有分子机械运动产生的内在机械信号的人工细胞外基质鲜有报 道. 在此, 我们报道了含光诱导片段定向滑动的机械动态水凝胶的合成及其作为人工细胞外基质在调节胚胎干细胞(ESC)分化中的功能. 通过引入光笼蔽的半胱氨酸残基调控亲疏水交替多肽的自 组装制备机械动态水凝胶. 光笼蔽多肽组装体在光照射下转化为热力学非平衡的非笼蔽多肽双分子层, 其进一步发生热力学有利的疏水性塌陷转变诱导的片段定向滑动. 在机械动态水凝胶上培养鼠胚胎干细胞, 该片段定向滑动诱导干细胞向外胚层谱系定向分化. 进一步揭示了机械动态水凝胶促进机械转导蛋白YAP进入细胞核, 表明其用于ESCs定向分化的潜在机械转导机制. 细胞定向分化结果表明了机械动态水凝胶作为潜在的生物材料, 有望用于疾病治疗和组织再生.

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Acknowledgements

This work was supported by the National Key R&D Program of China (2018YFC1313003), the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (21774065 and 31622038), and the Natural Science Foundation of Tianjin (18JCQNJC14100 and 18JCJQJC48400).

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Functional Polymer Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China

    Zhifei Cheng  (程志非), Shuxin Song  (宋树鑫) & Zhilin Yu  (余志林)

  2. State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, National Demonstration Center for Experimental Biology Education and College of Life Sciences, Nankai University, Tianjin, 300071, China

    Shanshan Nai  (能姗姗) & Lingyi Chen  (陈凌懿)

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  1. Zhifei Cheng  (程志非)
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  2. Shanshan Nai  (能姗姗)
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  3. Shuxin Song  (宋树鑫)
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  4. Lingyi Chen  (陈凌懿)
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Contributions

Author contributions Cheng Z and Yu Z conceived and designed the study. Cheng Z and Song S carried out the preparation and characterization of the hydrogels. Nai S and Chen L designed and performed all the cellular studies. Cheng Z prepared the manuscript with assistance from Nai S. Chen L and Yu Z revised the manuscript. All the authors discussed the results and have the approval of the submission of the final version of the manuscript.

Corresponding authors

Correspondence to Lingyi Chen  (陈凌懿) or Zhilin Yu  (余志林).

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Conflict of interest The authors declare that they have no conflict of interest.

Additional information

Zhifei Cheng received his MSc degree from Hefei University of Technology in 2017. Then he continued his study as a PhD candidate under the guidance of Prof. Zhilin Yu at Nankai University. His current research interest focuses on the development of peptide-based dynamic materials for biomedical applications.

Shanshan Nai received her MSc degree from the College of Life Sciences, Capital Normal University in 2018. She is now a PhD student in Prof. Lingyi Chen’s laboratory at the College of Life Sciences, Nankai University. Her current interest focuses on novel Mek1 downstream targets in maintaining the pluripotency of embryonic stem cells.

Lingyi Chen is a professor and vice dean of the College of Life Sciences, Nankai University, and an awardee of the National Science Fund for Excellent Young Scholars. He obtained his PhD degree in biochemistry from Northwestern University in 2004, and then conducted his postdoctoral research in Harvard University. He established his laboratory at Nankai University in 2008, and his research interests include molecular mechanism of pluripotency maintenance in embryonic stem cells and molecular regulation of early mouse embryonic development.

Zhilin Yu was awarded his PhD degree under the supervision of Prof. Stefan Hecht at the Humboldt- Universität zu Berlin in 2013. He conducted his postdoctoral training with Prof. Samuel I. Stupp at Northwestern University focusing on self-assembly of peptide-based amphiphilic molecules. In 2017, he started his independent career at the Institute of Polymer Science of Nankai University. His current research interests focus on the self-assembly of peptides into dynamic nanostructures and their broad applications as biomaterials including disease diagnosis and therapy.

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40843_2019_1184_MOESM1_ESM.pdf

Photoinduced Directional Domain Sliding Motion in Peptide Hydrogels Promotes Ectodermal Differentiation of Embryonic Stem Cells

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Cheng, Z., Nai, S., Song, S. et al. Photoinduced directional domain sliding motion in peptide hydrogels promotes ectodermal differentiation of embryonic stem cells. Sci. China Mater. 63, 467–478 (2020). https://doi.org/10.1007/s40843-019-1184-y

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