Effect of N-terminal acetylation on lytic activity and lipid-packing perturbation induced in model membranes by a mastoparan-like peptide

ALVARES, DAYANE S.; WILKE, NATALIA; RUGGIERO NETO, JOÃO

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Año: 2018 vol. 1860 p. 737 - 748

0005-2736

L1A (IDGLKAIWKKVADLLKNT-NH2) is a peptide that displays aselective antibacterial activity to Gram-negative bacteria without beinghemolytic. Its lytic activity in anionic lipid vesicles was stronglyenhanced when its N-terminus was acetylated (ac-L1A). This modificationseems to favor the perturbation of the lipid core of the bilayer by thepeptide, resulting in higher membrane lysis. In the present study, weused lipid monolayers and bilayers as membrane model systems to explorethe impact of acetylation on the L1A lytic activity and its correlationwith lipid-packing perturbation. The lytic activity investigated in giantunilamellar vesicles (GUVs) revealed that the acetylated peptidepermeated the membrane at higher rates compared with L1A, and modifiedthe membrane´s mechanical properties, promoting shape changes. Thepeptide secondary structure and the changes in the environment of thetryptophan upon adsorption to large unilamellar vesicles (LUVs) weremonitored by circular dichroism (CD) and red-edge excitation shiftexperiments (REES), respectively. These experiments showed that the Nterminusacetylation has an important effect on both, peptide secondarystructure and peptide insertion into the bilayer. This was also confirmedby experiments of insertion into lipid monolayers. Compression isothermsfor peptide/lipid mixed films revealed that ac-L1A dragged lipidmolecules to the more disordered phase, generating a more favorableenvironment and preventing the lipid molecules from forming stiff films.Enthalpy changes in the main phase transition of the lipid membrane uponpeptide insertion suggested that the acetylated peptide induced higherimpact than the non-acetylated one on the thermotropic behavior ofanionic vesicles.