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

Abstract

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. To elucidate the interaction of a cationic surfactant synthesized in our lab, investigations involving N α -benzoyl-arginine decyl amide (Bz-Arg-NHC 10 ), and model membranes composed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were done. Bz-Arg-NHC 10 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-NHC 10 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-NHC 10 . DPPC bilayer patches were partially removed, mainly in borders and bilayer defects for 50 µM Bz-Arg-NHC 10 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 explained by Bz-Arg-NHC 10 adsorption. When patchy DPPC bilayers were formed on the substrate, a SPR signal net decrease was obtained, which is consistent with the phospholipids' removal observed in the AFM images. 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.

Candidicidal Effect of Arginine-based Surfactants

“…Studies involving the interaction of Bz-Arg-NHC 10 with dipalmitoylphosphatidylcholine (DPPC) model membranes had been carried out previously in order to explain the enhanced antibacterial activity of this compound (Hermet et al 2021). Those experiments enabled the calculation of the MIP for DPPC monolayers at the same surfactant concentration used in the present work (30 µM).…”

“…The results reported by those authors also suggested an antagonistic effect of the amino and guanidinium groups on the antifungal behavior of the arginine-based tensioactives studied: therefore, the presence of the amino group may partially neutralize the anticandida action of the guanidinium group(Pérez et al 2021). This effect seemed to be compensated in the example of our compounds, since the benzoyl group attached to the amino-acid moiety increases the molecule's hydrophobicity(Hermet et al 2021). This greater hydrophobicity becomes relevant in view of the previously discussed mode of action of cationic surfactants: hydrophobicity enhances the molecule's a nity for the membrane phase, thus improving ability of the former to insert itself within the lipidic regions(Fonseca et al 2010).…”