Influence of Lipid Composition on Membrane Activity of Antimicrobial Polymers

HDPs and their synthetic analogs selectively lyse bacteria cells instead mammalian cells. The mechanism by which these molecules interact with the cell membranes is still unclear, although several models have been proposed. The membrane selectivity of the HDPs strongly depends on chemical and structural properties of the lipids, which form the different cell membranes. Most of the bacterial membranes are composed of PE & PG lipids, whereas the outer surface of mammalian red blood cells (RBCs) is rich in PC lipids. To elucidate the importance of individual lipid types on the membrane activity of HDP mimics, ten different antimicrobial polymers (Poly 1 ? 9) and one oligomer (10) were studied. Interactions of these antimicrobial macromolecules (AMMs) with different phospholipids composition Calcein vesicles were characterized using a fluorescent dye leakage assay. Poly 1, Poly 4 & Poly 5 remained inactive against all of the vesicles. The results also indicated that a certain percentage of PE lipids are extremely necessary for the membrane activity of the polymers (Poly 2 and Poly 6 ? 10). In contrast, Poly 3 remained equally active against all of the different vesicles. These observations provide an unconventional insight that lipid type and structure are critically more important than lipid head group charges for selective membrane interactions.

Abbreviations and keywords

Host Defense Peptides (HDPs), HDP mimic compounds, vesicle, phospholipids bilayer membrane, antimicrobial macromolecules (AMMs), Red Blood Cells (RBCs), Calcein, Phosphatidylcholine (PC), Phosphatidylglycerol (PG), Phosphatidylethanolamine (PE).