The mechanism of action of membrane disrupting antimicrobial peptides (AMPs) and the basis of their specificity and selectivity to pathogens are often studied by using biomimetic model membranes. It is often assumed that all model membrane morphologies, e.g. liposomes, supported bilayers, tethered bilayers etc. are equivalent. In this work the validity of this assumption was assessed. Melittin was used as the reference AMP as it can disrupt both bacterial and mammalian-mimetic membranes. Quartz crystal microbalance (QCM) viscoelastic fingerprints show characteristic differences between the three model morphologies: single bilayer membranes, multilamellar membrane stacks and unilamellar liposomes. In the second and third case, initial trends show material removal instead of material addition as in the single bilayer case, consistent with dissolution of some bilayers, and bursting liposomes, respectively. The latter is accompanied by a characteristic drop in the dissipation signal as the liposomes collapse. The results also highlight an important limitation of the QCM method, the need for a well established reference system for qualitative analysis of the viscoelastic fingerprints, and thus the importance of using the right model system, i.e. single bilayer membrane, for studies of the mechanism of action of AMPs.
