J Am Chem Soc. 2019 Mar 27;141(12):4886-4899. doi: 10.1021/jacs.8b13363. Epub 2019 Mar 12.
Short peptides are uniquely versatile building blocks for self-assembly. Supramolecular peptide assemblies can be used to construct functional hydrogel biomaterials-an attractive approach for neural tissue engineering. Here, we report a new class of short, five-residue peptides that form hydrogels with nanofiber structures. Using rheology and spectroscopy, we describe how sequence variations, pH, and peptide concentration alter the mechanical properties of our pentapeptide hydrogels. We find that this class of seven unmodified peptides forms robust hydrogels from 0.2-20 kPa at low weight percent (less than 3 wt %) in cell culture media and undergoes shear-thinning and rapid self-healing. The peptides self-assemble into long fibrils with sequence-dependent fibrillar morphologies. These fibrils exhibit a unique twisted ribbon shape, as visualized by transmission electron microscopy (TEM) and Cryo-EM imaging, with diameters in the low tens of nanometers and periodicities similar to amyloid fibrils. Experimental gelation behavior corroborates our molecular dynamics simulations, which demonstrate peptide assembly behavior, an increase in β-sheet content, and patterns of variation in solvent accessibility. Our rapidly assembling pentapeptides for injectable delivery (RAPID) hydrogels are syringe-injectable and support cytocompatible encapsulation of oligodendrocyte progenitor cells (OPCs), as well as their proliferation and three-dimensional process extension. Furthermore, RAPID gels protect OPCs from mechanical membrane disruption and acute loss of viability when ejected from a syringe needle, highlighting the protective capability of the hydrogel as potential cell carriers for transplantation therapies. The tunable mechanical and structural properties of these supramolecular assemblies are shown to be permissive to cell expansion and remodeling, making this hydrogel system suitable as an injectable material for cell delivery and tissue engineering applications.
短肽是自组装的独特多功能构建块。超分子肽组装可用于构建功能性水凝胶生物材料 - 这是神经组织工程的一种有吸引力的方法。在这里，我们报告了一类新的短五残基肽，它们形成具有纳米纤维结构的水凝胶。使用流变学和光谱学，我们描述了序列变化，pH 值和肽浓度如何改变我们的五肽水凝胶的机械性能。我们发现，这一类七个未修饰的肽在细胞培养基中以低重量百分比（小于 3wt％）形成从 0.2-20kPa 的坚固水凝胶，并经历剪切变薄和快速自修复。这些肽自组装成具有序列依赖性纤维形态的长原纤维。这些原纤维通过透射电子显微镜（TEM）和 Cryo-EM 成像呈现独特的扭曲带状形状，直径在数十纳米范围内，周期性与淀粉样纤维相似。实验凝胶化行为证实了我们的分子动力学模拟，该模拟演示了肽组装行为，β-折叠含量增加以及溶剂可及性变化的模式。我们的可注射递送（RAPID）水凝胶的快速组装五肽（RAPID）是可注射的，支持少突胶质前体细胞（OPC）的细胞相容性封装，以及它们的增殖和三维过程延伸。此外，RAPID 凝胶可保护 OPC 免受机械膜破坏和从注射器针头射出时的急性活力丧失，突出了水凝胶作为移植治疗潜在细胞载体的保护能力。这些超分子组装的可调机械和结构性质被证明允许细胞扩展和重塑，使该水凝胶系统适合用作细胞递送和组织工程应用的可注射材料。
