Unveiling theInteractions between Amino Acids-BasedSurfactants and Lipid Bilayers: A Small Angle Neutron Scattering andReflectivity Study

<i>N</i>-Acyl amino acids are biodegradable anionic amphiphilic molecules made up of linear fatty acids as hydrophobic tails and amino acids as polar heads, which are promising for their applicability in different technological fields. In the light of widening their use, a deeper understanding of their interactions with biological membranes is required, especially to further assess their toxicological profile. We investigated the interaction between <i>N</i>-decanoyl amino acid surfactants and phospholipid bilayers as simple <i>in vitro</i> models for biological membranes in comparison to sodium dodecyl sulfate using neutron scattering techniques. The information from small angle neutron scattering (SANS, <i>q</i> range from 0.008 to 0.25 Å^–1) focusing on liposome-to-surfactant interactions and neutron reflectivity (NR, <i>Q</i> range measured at three incident angles θ = 0.35, 0.65, and 1.5°) focusing on lipid bilayer-to-surfactant interactions was combined to provide a detailed characterization. All amino acid surfactants (C₁₀-alanine, C₁₀-glycine, C₁₀-leucine, C₁₀-methionine, C₁₀-serine, and C₁₀-proline) exhibited a similar behavior in terms of incorporation in liposomes and lipid removal as well as adsorption profiles in bilayers up to their critical micelle concentration (CMC). Notably, bilayer destabilization occurred for all surfactants (except for C₁₀-serine and C₁₀-alanine) at a concentration between CMC and 2× CMC. Such a result demonstrates the exceptional ability of C₁₀-serine and C₁₀-alanine to integrate into bilayers without disruption up to concentrations as high as ∼3–4× CMC. These findings support the lower cytotoxic effect of C₁₀-serine and C₁₀-alanine surfactants, observed in previous studies, and provide new insights on the mechanism of interaction of <i>N</i>-decanoyl amino acids with lipid membranes.