Membrane-active peptides are often classified to act either specifically or unspecifically. The binding to a component of the target membrane or the formation oligomeric channnels are, for example, considered specific effects. Unspecific action may refer to the induction of curvature stress within and between the lipid leaflet(s). The term �detergent like action� is sometimes used to describe mixed micelle formation although detergents typically permeabilize membranes by forming toroidal pores or membrane defects at concentrations well below those required for micellization.Here we discuss a scenario that is intermediate between these classical, extreme cases and explains selectivity and high activity of, for example, lipopeptide biosurfactants. It results from the fact that principally unspecific membrane perturbation can be boosted if the perturbant is not diluted homogeneously over the membrane but sequestered into domains at high local concentration. While the destabilizing effect as such is unspecific, the interactions triggering segregation can result from specific immiscibility with certain membrane components (e.g., cholesterol). Cofactors that enhance or enhance or diminish membrane heterogeneity may enhance or inhibit the activity of such 'unspecific' membrane perturbants.

Effects governing the activity and selectivity of membrane-permeabilizing lipopeptides

245th National Meeting (2013)

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