Effect of Arginine-based Surfactant on Model Membranes of Bacteria and Mammalian Virus

SABATIE, A.; HERMET, M.; FAIT, M.E.; MORCELLE, S.R.; FANANI, M.L.

Córdoba

Congreso; LI Reunión Anual de la Sociedad Argentina de Biofísica; 2023

Arginine-based surfactants, as cationic amphiphiles, have an intrinsic biocidal activity against viruses, bacteria and fungi. We have synthesized in our laboratory an arginine alkyl-amide (ArgC12) which has been characterized as a broad spectrum antimicrobial agent. The biocidal mechanism described for this kind of compounds involves its interaction with the cytoplasmic membrane. The aim of this work was to deepen into this mechanism using in vitro model membranes.Liposomes were prepared using an E. coli lipid extract (ECEx) and a mammalian-like lipid mixture (POPC/16:0 SM/Cho 1:1:1, MVM) for bacterial and enveloped mammalian-like virus membrane models respectively. ArgC12 was a stronger inducer of the content leakage of MVM liposomes, measured as the release of carboxyfluorescein (CF50% of 79.3 and 289.7 μM for MVM and ECEx, respectively), evidencing a differential interaction in each case. Our compound also induced membrane fusion, which may be related to the neutralization of surface charges. Additionally, MVM liposomes evidenced membrane disruption at high surfactant concentrations. Fluorescence studies also suggested that the structure of the membrane bound water and the membrane microviscosity were altered upon ArgC12 insertion, with saturation at a lipid/surfactant ratio of 1:3.On the other hand, penetration of ArgC12 into the model lipid monolayers indicated that the surfactant could be incorporated in both membranes to a similar extent, which suggested that the differences found in the surfactant-treated liposomes are not a consequence of differential amphiphile’s incorporation.Finally, we found that after the insertion of ArgC12 into the ECEx monolayers the membrane became less compressible and more surface-unstable. Contrarily, when the surfactant was inserted into the MVM monolayers, it induced a more compressible and stable membrane. This finding may be related to the differential resistance of both lipid membranes to ArgC12-induced content leakage.