Mimicking the receptor-aided binding of HIV-1 TAT protein transduction domains to phospholipid monolayers at the air-water interface

Abstract

We have designed heparin-incorporated model lipid monolayers and monitored the adsorption behaviours of cell penetrating peptides (CPPs) on a molecular scale at the air-water interface. We found initially that heparin could incorporate homogeneously into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS), and DPPC/DPPS mixed monolayers, allowing improved adsorption of transcription-activating factor (TAT) derived peptide (TAT-TDP) molecules. X-ray reflectivity measurements, as well as the surface pressure changes from surface pressure-area isotherms, suggest that a preferred interaction of heparin with TAT-TDP occurs, and is responsible for the effective penetration. This behaviour resembles the ubiquitous activities of glycosaminoglycan (GAG) molecules as cellular receptors that promote intracellular transport of cell-penetrating peptide domains in biological systems. We suggest that heparin-TAT-TDP complex formation can be exploited in a primary step of CPP translocation.