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 C(Glu)C and single-chain amphiphile CGlu with the model biomembrane formed by the phospholipid 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC). The partition coefficients of C(Glu)C and CGlu 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 CGlu, the molecules form shorter wormlike micelles with a lower surface charge at all the pHs and temperatures used, and the partition coefficient of CGlu into the DOPC vesicles does not change with temperature and pH. Differently, the C(Glu)C 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 C(Glu)C 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, C(Glu)C shows a stronger partition ability than CGlu. 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.