Physical properties affecting cochleate formation and morphology using antimicrobial oligo-acyl-lysyl peptide mimetics and mixtures mimicking the composition of bacterial membranes in the absence of divalent cations

Abstract

Several cationic antimicrobial oligo-acyl-lysyl (OAK) peptide mimetics can form cochleate structures, that is, elongated multilayered cylindrical structures, with lipid mixtures mimicking the composition of bacterial cytoplasmic membranes. These cochleate structures do not require divalent cations for their assembly. In the present work, we use light microscopy to screen for cochleate formation in several OAK-lipid systems and freeze-fracture electron microscopy to assess their morphological features and size. We identify several factors that facilitate a structural change in these assemblies. Dehydration of the membrane interface and a high melting temperature are features of the lipids that enhance cochleate formation in OAK-based lipid systems. In addition, we observed that there is a specific length of the hydrocarbon linker in the OAK of 8-9 carbon atoms that provides optimal formation of these structures. The biophysical properties established in this study will allow for a better understanding of their role and suitability for biological studies.