Design and Characterization of Nucleopeptides for Hydrogel Self-Assembly

Self-assembling peptides can be used in a bottom-up approach to build hydrogels that are similar to the extracellular matrix at both structural and functional levels. In this study, a nucleo-tripeptide library was constructed to identify molecules that form hydrogels under physiological conditions. We used both experimental and computational approaches to study these self-assembled structures. Circular dichroism spectroscopy, transmission electron microscopy, and rheometry were utilized to support and supplement molecular dynamics simulations. Our data demonstrate that nucleo-tripeptides can form nanofibrous hydrogels through Watson-Crick base pairing and π-π stacking interactions. Self-assembly conditions are mediated by nucleo-tripeptide hydrophobicity and amphiphilicity and can therefore be regulated by a rational molecular design. We have found that structures derived from specific peptide and nucleobase conjugations form hydrogels under physiologic conditions, making them promising candidates for biomedical applications.