Development of New Fluorescence Methods for the Characterization of Pores Formed by Antimicrobial Peptides

Abstract: Antimicrobial peptides, AMPs, disrupt biological membranes with the possible consequence of cell death. They have raised much interest as possible alternatives to conventional antibiotics. One main mechanism for the function of AMPs is the formation of membrane pores. Since these pores are not stable structures and are smaller than the resolution of an optical microscope, methods unambiguously proofing the existence of those pores for a specific AMP are missing. Our aim is to develop new methods for characterization of antimicrobial pores, based on two fluorescence concepts: Donor-donor energy migration and environmental-based shifts in fluorescence emission. Fluorescent lipid probes with conic-like structure will be used. Such dyes are supposed to have high affinity to highly curved regions and thus serve as pore-markers. The probes will be synthesized in a partner lab. We will test their aggregative behaviour in model systems with high and low curvature and in membranes containing real antimicrobial pores. Finally, this new concept will be used to elucidate action of new AMPs.