Protein Transduction Domain Mimic (PTDM) Self-Assembly?

Intracellular protein delivery is an invaluable tool for biomedical research, as it enables fundamental studies of cellular processes and creates opportunities for novel therapeutic development. Protein delivery reagents such as cell penetration peptides (CPPs) and protein transduction domains (PTDs) are frequently used to facilitate protein delivery. Herein, synthetic polymer mimics of PTDs, called PTDMs, were studied for their ability to self-assemble in aqueous media as it was not known whether self-assembly plays a role in the protein binding and delivery process. The results obtained from interfacial tensiometry (IFT), transmission electron microscopy (TEM), transmittance assays (%T), and dynamic light scattering (DLS) indicated that PTDMs do not readily aggregate or self-assemble at application-relevant time scales and concentrations. However, additional DLS experiments were used to confirm that the presence of protein is required to induce the formation of PTDM-protein complexes and that PTDMs likely bind as single chains.