Curvature Engineering: Positive Membrane Curvature
Induced by Epsin N‑Terminal Peptide Boosts Internalization
of Octaarginine
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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
(R<sub>8</sub>), 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 R<sub>8</sub> and EpN18, thus emphasizing the
importance of positive curvature induction for achieving the desired
ultimate cargo bioavailability