Significance of cellular surface factors for the selective cytotoxicity of antimicrobial peptides (AMPs) against cancer cells

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The objectives of this project are to gain an understanding of the dynamics of the interactions of antimicrobial peptides with human cancer cells and the molecular basis for differential cytotoxicity and mode of action based on the hypothesis that the presence and/or shape of the cellular surface (glyco)-structures have a significant impact on peptide-cell interaction. We will comprehensively analyse peptide interactions with human cancer cell lines, which naturally or artificially differ in the surface exposition of negatively charged glycans (e.g. sialic acids) or in the thickness of the glycocalyx. The core instrumentation of this application is a metabolic chip biosensor, which enables the assessment of the dynamics of important cell physiological parameters. To correlate the biological activities of peptides with the presence and chemical structure of cellular surface molecules, the biological data will be complemented by peptide-membrane interaction studies, e.g. membrane binding, intercalation, and permeabilization, using artificial membranes composed of phospholipids and glycolipids to mimic the differently composed membranes of normal and aberrant cells.