Adsorption Behavior of C10 Amino Acid Surfactants at the Air/Water Interface: Implications for Membrane Compatibility
TL;DR
It is demonstrated that interfacial packing provides a useful structural framework for rationalizing the membrane behavior of closely related amino acid-based surfactants, while highlighting that additional molecular factors are likely to contribute to surfactant–membrane interactions.
Abstract
Amino acid-based surfactants represent a promising class of biocompatible and biodegradable amphiphiles with increasing relevance in pharmaceutical and biomedical applications. Despite their growing use, a quantitative understanding of their interfacial packing and how this relates to membrane interactions remains limited. Here, we combine surface tension measurements and neutron reflectivity (NR) to determine the area per molecule (APM), adsorbed amount (Γ), and interfacial structure of a series of C10-based N-acyl amino acid surfactants (C10-Leu, C10-Ser, and C10-Ala) at the air/buffer interface. NR reveals monolayers of comparable thickness (∼23.5 Å) for all surfactants, but with significant differences in packing density: C10-Leu exhibits the largest APM due to its bulky headgroup, whereas C10-Ser forms the most compact monolayer, likely stabilized by its hydroxyl-containing side chain. For C10-Ser and C10-Leu, APM values derived from NR were consistent with surface tension results, while NR resolved the uncertainty in the APM of C10-Ala from tensiometric measurements owing to its greater structural sensitivity. The interfacial packing characteristics correlate with the membrane behaviors previously observed within the C10 amino-acid surfactant series: surfactants with smaller APM and higher packing density (e.g., C10-Ser) were incorporated into lipid bilayers to a greater extent and were tolerated at higher concentrations before membrane disruption occurred, whereas surfactants with bulkier headgroups (e.g., C10-Leu) exhibited reduced incorporation and induced membrane disruption at lower concentrations. Measurements at 25 and 37 °C showed no significant temperature dependence. These findings demonstrate that interfacial packing provides a useful structural framework for rationalizing the membrane behavior of closely related amino acid-based surfactants, while highlighting that additional molecular factors are likely to contribute to surfactant–membrane interactions.