Figure 1.

The mechanistic landscape of membrane permeabilizing peptides. The molecular mechanisms of membrane permeabilizing peptides have, for the most part, eluded atomic level description despite decades of intense study. As a result, their active structures and mechanisms are often drawn as cartoons like the imaginary snapshots arrayed in the cartoon bilayer above. Different colored lipids indicate changes in membrane composition, lipid tails and headgroups. Curvy tails indicate fluid phase bilayers and straight tails indicate more ordered domains. In this review we describe how it might be useful to think of membrane permeabilizing peptides on a mechanistic landscape where molecular mechanism is not a fixed entity, but instead depends on the sum of many experimental variables. The image in the center of the cartoon vesicle depicts concentric “dials”, one for each experimental variable (many are not explicitly shown). Each dial can be set to a particular “value” in the parameter space. The combinations of all the settings give rise to a point on multidimensional mechanistic landscape.