A β-sheet structure interacting peptide for intracellular protein delivery into human pluripotent stem cells and their derivatives

The advance in stem cell research relies largely on the efficiency and biocompatibility of technologies used to manipulate stem cells. In our previous study, we had designed an amphipathic peptide RV24 that can deliver proteins into cancer cell lines efficiently without significant side effects. Encouraged by this observation, we moved forward to test whether RV24 could be used to deliver proteins into human embryonic stem cells and human induced pluripotent stem cells. RV24 successfully mediated protein delivery into these pluripotent stem cells, as well as their derivatives including neural stem cells and dendritic cells. Based on NMR studies and particle surface charge measurements, we proposed that hydrophobic domain of RV24 interacts with β-sheet structures of the proteins, followed by formation of “peptide cage” to facilitate delivery across cellular membrane. These findings suggest the feasibility of using amphipathic peptide to deliver functional proteins intracellularly for stem cell research.

► An amphipathic peptide RV24 delivers proteins into human pluripotent stem cells. ► RV24 also delivers proteins into cells derived from the pluripotent stem cells. ► RV24 forms complex with protein through hydrophobic interaction, as shown by NMR. ► Protein β-sheet is essential for complex formation between RV24 and protein.