The study shows that two pieces of the human antimicrobial peptide LL-37 behave very differently when they sit at a surface. The longer piece (LL-32) folds into a stable alpha‑helix and sticks strongly to the surface, which matches its stronger ability to kill microbes. The shorter piece (LL-20) stays mostly floppy and doesn’t bind as well, which explains why it’s much less effective.

Two fragments of the antimicrobial peptide LL-37 (LL-32 and LL-20) have been characterized in adsorption layers at the air/buffer interface by infrared reflection absorption spectroscopy (IRRAS) and X-ray reflectivity (XR) measurements. As shown in previous work, LL-32 exhibits an increased antimicrobial activity compared to LL-37, while LL-20 is almost not active. It is shown in this work that the peptides differ drastically in their surface activity (equilibrium adsorption pressure) and their secondary structure, when they are adsorbed to the air/buffer interface. As concluded from the CD spectra, both peptides are unstructured in bulk. That means that the adsorption of the peptides to the air/buffer interface is connected to a secondary structure change. While LL-32 transforms into an α-helix lying flat at the buffer surface, with a helix diameter of 17Å, LL-20 adopts a partly unstructured conformation. The dichroic ratio of LL-20 is reduced and the electron density profile shows the formation of a second layer. The ability of LL-32 to form a complete α-helical structure at the interface is in good agreement with its higher antimicrobial activity.