PEPTIDE SELF-ASSEMBLY INTO SUPRAMOLECULAR HYDROGELS FOR CELL SPHEROID MORPHOGENESIS

Hydrogels are supramolecular architectures that emulate the topology and the chemical milieu of the extracellular matrix (ECM), resulting in more realistic mimics for in vivo conditions. In this communication, I present a recent study from our laboratory1 investigating the hydrogelation behavior of a designed decapeptide with bolaamphiphilic characteristics where a tetraleucine self-assembling backbone is flanked by fibronectin-related tripeptides at both termini. This synthetic sequence forms hydrogelled matrices entrapping >99% wt/vol % water. Ultrastructural analyses combining atomic force microscopy, small-angle neutron scattering, and fiber X-ray diffraction revealed amyloid-like nanofibrils forming cross-linked networks endowed with high thermal stability, the structure of which is not disrupted up to temperatures >80 °C. We also examined the interaction of peptide hydrogels with either NIH3T3 mouse fibroblasts 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 preparing highly stable scaffolds simultaneously endowed with high water retention capacity and the ability to instruct cell growth into tumor-like spheroids.