Influence of Sugar Headgroup on the Self-Assembly of Bioinspired Anionic Glycolipids

In this study, we investigated the micellization of bioinspired anionic glycolipids with distinct headgroups (xylose, rhamnose, and galactose) using surface tension, small-angle X-ray scattering (SAXS), and isothermal titration calorimetry (ITC) measurements across a range of temperatures. Surface and interfacial analyses revealed that their critical micelle concentration (CMC) is strongly influenced by the hydrophilicity of their sugar headgroups. SAXS data demonstrated that the aggregates are ellipsoidal micelles, with size and distortion influenced by their headgroup structure. Thermodynamic analyses indicate that micellization is driven by a delicate balance between enthalpic and entropic contributions, both being significantly affected by the sugar ring architecture, particularly the nature of the substituent at the C5 position. These findings show that the chemical features of the headgroup strongly influence the aggregate structure and micellization energetics of ionic glycolipids, providing relevant molecular-level insights for the rational design of new bioinspired amphiphiles.