Nanostructure Formation and Cell Spheroid Morphogenesis of a Peptide Supramolecular Hydrogel

Peptide-based hydrogels have attracted much attention due to their extraordinary applications in biomedicine and offer an excellent mimic for the 3D microenvironment of the extracellular matrix. These hydrated matrices comprisefibrousnetworks held together by a delicate balance of intermolecularforces. Here, we investigate the hydrogelation behavior of a designed decapeptide containing a tetraleucine self-assemblingbackbone andfibronectin-related tripeptides near both ends of the strand. We have observed that this synthetic peptide can producehydrogel matrices entrapping >99% wt/vol % water. Ultra-structural analyses combining atomic force microscopy, small-angle neutron scattering, and X-ray diffraction revealed thatamyloid-likefibrils form cross-linked networks endowed with remarkable thermal stability, the structure of which is not disrupted upto temperatures >80 degrees C. We also examined the interaction of peptide hydrogels with either NIH3T3 mousefibroblasts or HeLa cells and discovered that the matrices sustain cell viability and induce morphogenesis into grape-like cell spheroids. The results presented here show that this decapeptide is a remarkable building block to prepare highly stable scaffolds simultaneously endowed with highwater retention capacity and the ability to instruct cell growth into tumor-like spheroids even in noncarcinoma lineages

Automated summary

Peptide-based hydrogels are promising biomaterials that can mimic the 3D microenvironment of the extracellular matrix. This study demonstrates that a synthetic decapeptide can form highly stable hydrogel matrices that retain a high water content and induce morphogenesis in interacting cells.