Visualization of diffusion limited antimicrobial peptide attack on supported lipid membranes

Understanding the mechanism of action of antimicrobial peptides (AMP) is fundamental to the development and design of peptide based antimicrobials. Utilizing fast-scan atomic force microscopy (AFM) we detail the attack of an AMP on both prototypical prokaryotic (DOPC:DOPG) and eukaryotic (DOPC:DOPE) model lipid membranes on the nanoscale and in real time. Previously shown to have a favourable therapeutic index, we study Smp43, an AMP with a helical-hinge-helical topology isolated from the venom of the North African scorpion Scorpio maurus palmatus. We observe the dynamic formation of highly branched defects being supported by 2D diffusion models and further experimental data from liposome leakage assays and quartz crystal microbalance-dissipation (QCM-D) analysis, we propose that Smp43 disrupts these membranes via a common mechanism, which we have termed ‘diffusion limited disruption’ that encompasses elements of both the carpet model and the expanding pore mechanism.