Stimuli-Responsive, Pentapeptide, Nanofiber Hydrogel for Tissue Engineering

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. Experimen...