(A) HDPs and defensins first associate with the cell membrane via electrostatic charge interactions. (B) In the barrel stave model, the HDPs embed themselves through the membrane, forming a pore completely lined with peptide. (C) In the toroidal pore model, the HDPs force the lipid membrane to curve and form a continuous lipid layer. The pore is lined with lipid head groups and peptide. (D) In the carpet model, the HDPs spread over the surface of the membrane like a surfactant until a critical concentration is reached at which point, micelles are formed that as the membrane breaks apart. (E) In the NaD1–PA carpet model, NaD1 monomers cross the membrane before engaging PA and forming dimers that assemble into the MDC. The MDC induces membrane curvature stress and subsequent membrane rupture. (F) In the defensin membrane disruption model (as exemplified by NaD1 and NsD7), defensin monomers cross the membrane before engaging PI(4,5)P₂ and forming dimers that oligomerise into arch-shaped assemblies to induce membrane rupture. The defensins may also act from the extracellular membrane surface in some cases as abnormal cells such as in cancer often demonstrate disrupted membrane asymmetry.