Unraveling the mechanisms of peptide hydrogel assembly through molecular dynamics simulations of peptide pairs in water system

Peptide hydrogels possess special three-dimensional viscoelastic structures. They are ideal materials that could be used in drug delivery, tissue engineering and many other major biomedical fields. However, the underlying mechanism for peptide self-assembly is still not clear, hindering our ability to design peptide hydrogels for specific properties. It is also intriguing that a slight change in peptide sequence can significantly affect the gelling properties of the peptide. In this work, we use computational tools to simulate the pair interaction between hexapeptides of various sequences and investigate how the surrounding water molecules mitigate the inter-peptide interactions. The results are corroborated with experimental observations of the self-assembly of the same peptides. Our results show that (1) gelling occurs when there are strong, specific interactions between peptide pairs; and (2) while water is slowed down around single peptides, they are released when the peptide binds. These suggest that the gelling is likely to be an entropy-driven process.