Partition of Glutamic Acid-Based Single-Chain and Gemini Amphiphiles into Phospholipid Membranes

Understanding the interactions of amphiphile molecules with biological membranes is very important to many practical applications. Amino acid amphiphiles are a kind of mild surfactants and have many unique performances. However, their interactions with phospholipid membranes have scarcely been studied. This work has studied the interactions of glutamic acid-based gemini amphiphile C₁₂(Glu)₂C₁₂ and single-chain amphiphile C₁₂Glu with the model biomembrane formed by the phospholipid 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC). The partition coefficients of C₁₂(Glu)₂C₁₂ and C₁₂Glu into the DOPC vesicles were derived from the observed enthalpy curves obtained by isothermal titration calorimetry at temperatures of 25.0 and 37.0 °C, and pHs of 5.6 and 7.4, corresponding to the skin surface and human physiological conditions. The results from cryogenic transmission electron microscopy, dynamic light scattering, and zeta potential measurements show that the amphiphile molecules form different aggregates, which make the amphiphile molecules exhibit different partition abilities to the DOPC vesicles. For C₁₂Glu, the molecules form shorter wormlike micelles with a lower surface charge at all the pHs and temperatures used, and the partition coefficient of C₁₂Glu into the DOPC vesicles does not change with temperature and pH. Differently, the C₁₂(Glu)₂C₁₂ molecules form fibers with a larger negative charge and belts with a smaller negative charge at pHs 7.4 and 5.6, respectively, no matter what temperature is used. As a result, the partitions of C₁₂(Glu)₂C₁₂ into the DOPC vesicles are markedly different at these two pH values, and the belts at pH 7.4 exhibit a stronger partition ability than the fibrils at pH 5.6. Moreover, at any temperature and pH, C₁₂(Glu)₂C₁₂ shows a stronger partition ability than C₁₂Glu. This work can help to understand the relationship between the molecular structure and aggregate structure of amino acid amphiphiles and their partition abilities into the biomembranes.