Fig. 1. Modes of action of HDPs.
HDPs appear to function either through pore formation by direct interaction with the cell membrane, or within cells after escape from vesicle-like bodies. Modes of pore formation include barrel-stave (A), toroidal (B), and carpet-like (C) models, while the vesicle-like body model involves endocytosis-based translocation (D). (A) In the barrelstave model, HDPs bind the target cell membrane and are inserted into the hydrophobic lipid core of the plasma membrane to form barrels. Thereafter, the cytoplasmic contents are leaked through transmembrane pores, resulting in cell lysis. (B) In the toroidal model, HDPs are inserted into the target cell membrane and the head group of the lipid monolayer aligned with HDPs is bent, forming transmembrane pores and resulting in cell death in conjunction with depolarization of the plasma membrane. (C) In the carpet-like model, HDPs cover the surface of the target cell membrane, destroying the plasma membrane and forming carpet-like micelles. The interaction of the cell membrane and HDPs leads to the formation of pores in the inner membrane, followed by cell lysis. (D) The vesicle-like bodies model is associated with endocytosis for uptake of large particles. Vesicle-like bodies, such as macropinosomes formed by inward folding of the outer membrane, contain HDPs and translocate into the cell. After endosomal escape for intracellular delivery of HDPs, these peptides act on intracellular targets.