Institute for Complex Molecular Systems , Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven , The Netherlands.
Fujifilm Manufacturing Europe B.V. , P.O. Box 90156, 5000 LJ Tilburg , The Netherlands.
Biomacromolecules. 2019 Jun 10;20(6):2360-2371. doi: 10.1021/acs.biomac.9b00353. Epub 2019 May 28.
Structurally and functionally well-defined recombinant proteins are an interesting class of sequence-controlled macromolecules to which different crosslinking chemistries can be applied to tune their biological properties. Herein, we take advantage of a 571-residue recombinant peptide based on human collagen type I (RCPhC1), which we functionalized with supramolecular 4-fold hydrogen bonding ureido-pyrimidinone (UPy) moieties. By grafting supramolecular UPy moieties onto the backbone of RCPhC1 (UPy-RCPhC1), increased control over the polymer structure, assembly, gelation, and mechanical properties was achieved. In addition, by increasing the degree of UPy functionalization on RCPhC1, cardiomyocyte progenitor cells were cultured on "soft" (∼26 kPa) versus "stiff" (∼68-190 kPa) UPy-RCPhC1 hydrogels. Interestingly, increased stress fiber formation, focal adhesions, and proliferation were observed on stiffer compared to softer substrates, owing to the formation of stronger cell-material interactions. In conclusion, a bioinspired hydrogel material was designed by a combination of two well-known natural components, i.e., a protein as sequence-controlled polymer and UPy units inspired on nucleobases.
结构和功能明确的重组蛋白是一类有趣的序列控制的大分子，可应用不同的交联化学方法来调节其生物学性质。在此，我们利用基于人胶原蛋白 I 的 571 个残基的重组肽（RCPhC1），并在其上功能化超分子 4 倍氢键尿嘧啶嘧啶酮（UPy）部分。通过将超分子 UPy 部分接枝到 RCPhC1 的主链上（UPy-RCPhC1），实现了对聚合物结构、组装、凝胶化和机械性能的更好控制。此外，通过增加 RCPhC1 上 UPy 功能化的程度，可以在“软”（约 26 kPa）和“硬”（约 68-190 kPa）UPy-RCPhC1 水凝胶上培养心肌细胞前体细胞。有趣的是，与较软的基质相比，在较硬的基质上观察到应力纤维形成、焦点黏附和增殖增加，这是由于形成了更强的细胞-材料相互作用。总之，通过组合两种众所周知的天然成分，即作为序列控制聚合物的蛋白质和受核碱基启发的 UPy 单元，设计了一种仿生水凝胶材料。
