One-step formulation of nonionic surfactant bicelles (NSBs) by a double-tailed polyglycerol-type nonionic surfactant

Bicelles are generally formed by phospholipid-based systems and are useful for various applications, such as nanocarriers or membrane protein crystallization. The same disc-like assemblies, nonionic surfactant bicelles (NSBs), can also be formed using nonionic amphiphiles, but this has not been reported extensively. We report a novel NSB system that employs the double-tailed nonionic amphiphile, polyglyceryl dialkyl ether (C₁₂C_mG_n), which has two alkyl chains and a polyglyceryl group. A symmetric-tail molecule, C₁₂C₁₂G_13.8, formed vesicles, whereas an asymmetric-tail molecule, C₁₂C₁₄G_15.5, formed NSBs through a simple one-step process using ultrasonication. The 1 wt% aqueous solution of C₁₂C₁₄G_15.5 was in a two-phase equilibrium of a lamellar phase and a water phase. Transparent dispersion was obtained through ultrasonication treatment. The size distribution in the dispersion was obtained by dynamic light scattering (DLS), resulting in a narrow distribution of around 20 nm in diameter. A negatively-stained transmission electron microscopy (TEM) image showed oblong and spherical shapes, which are typically observed in bicelle-forming systems. A small angle neutron scattering (SANS) measurement well proved bicelle formation by fitting a core-shell bicelle form factor model. The disc thickness and diameter were in agreement with the values obtained by DLS and TEM, respectively. A larger shell thickness at the rim part than at the flat disc part suggested that NSB aggregates have inhomogeneous molecular distribution. Similar to phospholipid systems, the bicelle-forming C₁₂C₁₄G_15.5 system produced a defective lamellar phase formation at high surfactant concentrations, whereas a general lamellar phase was formed in the vesicle-forming C₁₂C₁₂G_13.8 system.