Nanostructure formation and cell spheroid morphogenesis of a peptide supramolecular hydrogel

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2022-03-11
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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 comprise fibrous networks held together by a delicate balance of intermolecular forces. Here, we investigate the hydrogelation behavior of a designed decapeptide containing a tetra-leucine self-assembling backbone and fibronectin-related tripeptides near to both ends of the strand. We have observed that this synthetic peptide can to produce hydrogel matrices entrapping > 99% wt/vol% water. Ultrastructural analysis combining atomic force microscopy (AFM), small-angle neutron scattering (SANS) and X-ray diffraction revealed that amyloid-like fibrils form crosslinked networks endowed with remarkable thermal stability, the structure of which structure 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 prepare highly stable scaffolds simultaneously endowed with high water retention capacity and the ability to instruct cell growth into tumor-like spheroids even in non-carcinoma lineages.
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