Synthetic Short Peptides for Rapid Fabrication of Monolayer Cell Sheets

Cell sheets are useful materials in regenerative medicine; however, the cell sheet fabrication processes developed to date are associated with several crucial challenges. The aim of this study was to develop a new and simple method for the rapid and efficient fabrication of transferable monolayer cell sheets. Chemoenzymatic synthesis mediated by proteinase K was used to synthesize short co-oligopeptides for cell sheet fabrication, which showed high yield, well-defined structures, and a controllable composition. These co-oligopeptides predominantly adopted a random coil conformation in buffer. Histidine/cysteine co-oligopeptides with a disordered secondary structure displayed cysteine content-dependent esterase activity and cysteine content-independent protease activity. Taking advantage of this enzymatic activity, confluent cell monolayers were detached by simply adding the co-oligopeptides solution to the culture media, and then an intact monolayer cell sheet was prepared with high cell viability and rea...