Interaction of LL-37 human cathelicidin peptide with a model microbial-like lipid membrane

The only representative of cathelicidin peptides in humans is LL-37, a multifunctional antimicrobial pep-tide (AMP) that is a part of the innate immune response. Details of the LL-37 direct activity against patho-gens are not well understood at the molecular level. Here, we present research on the mechanism of interaction between LL-37 and a model multicomponent bilayer lipid membrane (BLM), mimicking microbial cell membrane. Electrochemical impedance spectroscopy (EIS), high-resolution atomic force microscopy (AFM) imaging, and polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) were applied to study the peptide influence on a model microbial-like membrane. We show that LL-37 causes changes in the phospholipid molecules conformation and orientation, leading to mem-brane disintegration, significantly affecting the membrane electrical parameters, such as capacitance and resistance. High-resolution AFM imaging shows topographical and mechanical effects of such disintegra-tion, while PM-IRRAS data indicates that introduction of LL-37 causes changes in the phospholipid acyl chains from all -trans to gauche conformations. Moreover, the presence of LL-37 significantly alters the value of the phospholipid tilt angle. Altogether, our results suggest a "carpet" membrane dissolution fol-lowed by a detergent-like membrane disruption mechanism upon LL-37 activity. This research gives a novel insight into the understanding of LL-37 influence on multicomponent model membranes and a promising contribution to the development of LL-37-derived therapeutic agents against drug-resistant bacteria. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).