Leakage and lysis of lipid membranes induced by the lipopeptide surfactin.

Surfactin is a lipopeptide produced by Bacillus subtilis which possesses antimicrobial activity. We have studied the leakage and lysis of POPC vesicles induced by surfactin using calcein fluorescence de-quenching, isothermal titration calorimetry and (31)P solid state NMR. Membrane leakage starts at a surfactin-to-lipid ratio in the membrane, R (b) approximately 0.05, and an aqueous surfactin concentration of C (S) (w) approximately 2 microM. The transient, graded nature of leakage and the apparent coupling with surfactin translocation to the inner leaflet of the vesicles, suggests that this low-concentration effect is due to a bilayer-couple mechanism. Different permeabilization behaviour is found at R (b) approximately 0.15 and attributed to surfactin-rich clusters, which can induce leaks and stabilize them by covering their hydrophobic edges. Membrane lysis or solubilization to micellar structures starts at R (b) (sat) = 0.22 and C (S) (w) = 9 microM and is completed at R (m) (sol) = 0.43 and C (S) (w) = 11 microM. The membrane-water partition coefficient of surfactin is obtained as K = 2 x 10(4) M(-1). These data resolve inconsistencies in the literature and shed light on the variety of effects often referred to as detergent-like effects of antibiotic peptides on membranes. The results are compared with published parameters characterizing the hemolytic and antibacterial activity.