Page - (000237) - in Biomedical Chemistry: Current Trends and Developments

3.1.3.1.1 AMPs: Mechanism of Action and Peptide Families Several models have been proposed for the mechanism of action of AMPs on membrane permeabilization or insertion, and this mechanism depends on a combination of hydrophobic and electrostatic effects (Shai, 1999; Sanderson, 2005). The most prominent models are the carpet mechanism, the barrel-stave model, and the toroidal pore model. Overall, the mechanism of interaction of AMPs with membranes results either in the translocation of peptides into the cell, the formation of pores embedded in the membrane to enable a flux of ions and molecules, or in membrane permeabilization/disruption (Fig. 3.1.10). Figure 3.1.10: Proposed mechanisms of AMP-mediated membrane disruption. A) Barrel-stave pore. Peptides insert perpendicularly in the bilayer, associate and form a pore. The peptides line the pore lumen in a parallel direction relative to the phospholipid chains, which remain perpendicular to the bilayer plane. B) Carpet mechanism. Peptides adsorb parallel to the bilayer and, after reaching sufficient coverage, produce a detergent-like effect that disintegrates the membrane. C) Toroidal pore. As with the barrel-stave pore, peptides insert perpendicularly in the bilayer, but instead of packing parallel to the phospholipid chains, the peptides induce a local membrane curvature in such a way that the pore lumen is lined partly by peptides and partly by phospholipid head groups. D) Disordered toroidal pore. A recent modification to the toroidal pore model proposes that less-rigid peptide conformations and orientations are formed, where the pore lumen is lined by the phospholipid head groups (adapted from Melo, 2009). The potency and range of the antimicrobial activity of AMPs vary