Assessment of the multiphase interaction between a membrane disrupting peptide and a lipid membrane

Although modeling and experimental approaches to probe antimicrobial peptides-lipid membranes interaction have already been reported, quantitative evaluation of the whole process, including full dissolution of the lipid, is still missing. We report on the real-time assessment of the entire set of stages of melittin-membrane interaction, based on surface plasmon resonance (SPR) measurements, using supported lipid matrices on L1 sensors and long peptide injections. We advance a mathematical model which comprises a set of coupled kinetic equations and relates via the transfer matrix the evolution of lipid and peptide concentrations with the SPR sensorgram. Upon fitting the sensorgrams of melittin injections on POPC lipid matrices, in agreement with literature data, the model provides: association and dissociation rates, concentration thresholds, and evolution within each interacting layer of lipid and peptide concentrations as well as of peptide to lipid ratios. The proposed model combined with appropriate experimental protocols adds new depths to SPR investigation of peptide-lipid interaction offering a quantitative platform for research and controlled design of improved antimicrobial peptides. A wider applicability for quantitative assessment of other pore forming compounds on different lipid matrices is suggested.