DSC studies on interactions between low molecular mass peptide dendrimers and model lipid membranes

Abstract

It has recently been shown that a newly synthesized peptide dendrimers possess antimicrobial activity against Gram-positive ( Staphylococcus aureus) and Gram-negative ( Escherichia coli) bacteria as well as against fungal pathogens ( Candida albicans) [Klajnert, B., Janiszewska, J., Urbanczyk-Lipkowska, Z., Bryszewska, M., Shcharbin, D., Labieniec, M., 2006. Biological properties of low molecular mass peptide dendrimers. Int. J. Pharm. 309, 208–217]. To extend our knowledge about their impact on biological systems, interactions between a group of low molecular mass lysine based dendrimers and model lipid bilayers were examined by differential scanning calorimetry (DSC). Conformational stability of dendrimers in 5–85 °C temperature range was confirmed by circular dichroism measurements (CD). The dendrimer structure has been shown to play an important role in interactions with the membranes. A two-step mechanism of dendrimer–bilayer interactions was proposed. The first step involves electrostatic attractions between dendrimers and polar lipid heads, while the second one is a result of hydrophobic interactions between acyl chains and arms of dendrimers. While one dendrimer did not interact with the membrane, another with long hydrophobic arms significantly perturbed the membrane. Nevertheless, for all tested dendrimers the main transition in DSC scans was retained that indicates that these compounds at the tested concentrations did not cause the loss of membrane integrity.