Cell penetrating peptides (CPPs) have a potential ability to transport physiologically active substances into cells. Most of the experiments have addressed the effects of amino acid sequence of CPPs on their transmembrane mechanism in the artificial liposome system. In contrast, the interactions between CPPs and lipids consisting of cell membranes are mainly studied through computational simulations. In order to elucidate those interactions experimentally, the reaction behavior of carboxyfluorescein (FAM)-labeled ε-poly-l-lysine (FAM-εPL) and octa-arginine (FAM-R8), which have the differently charged headgroup and hydrophobic acyl tails, was studied at the lipid monolayer-modified water|1,2-dichloroethane interfaces. FAM-R8 showed a high affinity for the lipid layer surface, whereas FAM-εPL predominately exhibited the phase transfer process. Nevertheless, the interfacial mechanism of FAM-εPL varied with the charge and structure of the lipid headgroup. The adsorption process of FAM-εPL became dominant for the lipid with multiple interaction points. It has been revealed that not only the structure of CPPs but also the properties of lipids play a key role in the transmembrane pathway.
Sakae et al. (2026) studied this question.