Curvature Engineering: Positive Membrane Curvature Induced by Epsin N‑Terminal Peptide Boosts Internalization of Octaarginine

Abstract

Epsin-1 is a representative protein for inducing the positive curvature necessary for the formation of clathrin-coated pits. Here we demonstrate that the N-terminus 18-residue peptide of epsin-1 (EpN18) has this ability <i>per se</i>, as proved by differential scanning calorimetry (DSC) and solid-state NMR. Moreover, it is shown how this positive curvature promotion can be exploited for promoting the direct penetration of a representative cell-penetrating peptide (CPP), octaarginine (R₈), through artificial and plasma membranes. This synergistic effect has been used for the efficient delivery of a proapoptotic domain peptide (PAD), which induced high level of apoptosis only when coadministered with R₈ and EpN18, thus emphasizing the importance of positive curvature induction for achieving the desired ultimate cargo bioavailability