Interaction of cationic surfactants with DPPC lipid membranes: effect of a novel Nα-benzoylated Arginine-based compound

HERMET, M.; FAIT, M.E.; VAZQUEZ, R.; MATÉ, S.; DAZA MILLONE, M.A.; VELA, M.E.; GARCÍA, M.T.; MORCELLE, S.R.; BAKÁS, L.

AMINO ACIDS

SPRINGER

Lugar: Berlin; Año: 2021

0939-4451

Cationic amino acid-based surfactants are known to interact with the lipid bilayer of microorganism resulting in cell death through a disruption of the membrane topology.In order to elucidate the interaction of a cationic surfactant synthesized in our lab, investigations involving Nα-benzoyl-arginine decyl amide (Bz-Arg-NHC10), and model membrane composed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were done. Firstly, the Bz-Arg-NHC10 micellization process was characterized in saline buffer. Bz-Arg-NHC10 was able to penetrate into DPPC monolayers up to a critical pressure of 59.6 mN./m-1. Differential scanning calorimetry revealed that as the concentration of Bz-Arg-NHC10 increased, the main transition temperature of DPPC slightly decreased. Atomic force microscopy (AFM) in situ experiments performed on supported DPPC bilayers on mica allowed monitoring the changes induced by Bz-Arg-NHC10. DPPC bilayer patches were partially removed, mainly in borders and bilayer defects for 50 µM Bz-Arg-NHC10 solution. Increasing the concentration to 100 µM resulted in a complete depletion of the supported bilayers. Surface plasmon resonance (SPR) experiments, carried out with fully DPPC bilayers covered chips, showed a net increase of the SPR signal, which can be assigned toexplained by Bz-Arg-NHC10 adsorption. When patchy DPPC bilayers were formed on the substrate, a net decrease of the SPR signal was obtained, which is consistent with the DPPC phospholipids? removal observed in the AFM images. Finally, a relationship between the micellization of this surfactant and the its mechanism of action on the lipid membrane is presented. The results obtained suggest that the presence of the benzoyl group attached to the polar head of our compound would be the responsible of the increased antimicrobial activity against Gram negative bacteria when compared with other arginine-based surfactants.