Interactions of cell penetrating peptide Tat with model membranes: A biophysical study

The protein transduction domain of the HIV-1 transactivator of transcription, Tat (Tat(48–60)), has been shown to transport P10, a cytotoxic peptide mimic of the cyclin dependent kinase inhibitor p21WAF1/CIP1, into the nucleus of cancerous cells and induce apoptosis. Here, monolayer studies were used to investigate the membrane interactions of Tat(48–60), P10 and the construct Tat(48–60)P10. It was found that Tat(48–60) showed no significant surface activity but that both P10 and Tat(48–60)P10, were highly surface active, inducing surface pressure changes of 9.7 and 8.9 mN m−1, respectively, with DMPS monolayers. The comparison of Tat(48–60)P10 and P10 surface interactions would be consistent with a hypothesis that the cargo attachment influences the capacity of the Tat-protein transduction domain to mediate transport across membranes either directly or via localisation of the construct at the membrane interface.