The crown ether size and stereochemistry affect the self-assembly, hydrogelation, and cellular interactions of crown ether/peptide conjugates.

The discovery of crown ethers and their unique interactions with ions make them play a key role in supramolecular chemistry. In this study, we have developed a new type of amphiphilic crown ether (DB18C6, DB24C8)-conjugated phenylalanine dipeptides for the gelation of water at physiological pH. We report here for the first time that the size of the crown ether controlled the morphology of the self-assembled nanostructures of the hydrogels, as well as their interactions with human mesenchymal stem cells (hMSCs; 3A6-RFP) and mouse fibroblasts (L929). For example, relative to its d-form and other crown sizes, DB18C6LFLF exhibited greater cell adhesion and was nontoxic towards hMSCs after culturing for 72 h. We hypothesize that the steric effect of the crown ether moiety in the assemblies has substantial influences on the morphology of the nanostructures and the cell-material response. Such distinct cell responses should be beneficial for the development of supramolecular biomaterials.