Structural Transitions in Self-Assembled Lipid Systems Driven by Induced Curvature: From Cell -Penetrating Peptides to Programmable Vesicles

Abstract

We also examined the interactions of other arginine rich cell-penetrating peptides, including Antp and oligoarginine, with model cell membranes, and find that the transduction activity correlates with induction of negative Gaussian curvature. The negative Gaussian membrane curvature is broadly enabling and its induction can lower the free energy barriers for a range of different entry mechanisms, such as direct translocation as well as endocytotic pathways. Furthermore, we show that the TAT peptide interacts strongly with actin cytoskeleton, which enhances membrane deformation and cytoskeleton reorganization necessary for endocytotic processes. We propose a mechanism that explains how a relatively simple molecule, like the TAT peptide, facilitates direct entry and multiple endocytotic mechanisms.