Block sequence affects thermosensitivity and nano-assembly: PEG-L-PA-DL-PA and PEG-DL-PA-L-PA block copolymers

We are reporting triblock copolymers of (ethylene glycol)(44)-(L-alanine)(9)-(DL-alanine)(9) (PEG-L-PA-DL-PA) with alpha-helical L-PA localized between flexible PEG and DL-PA, and (ethylene glycol)(44)-(DL-alanine) (9)-(L-alanine)(9) (PEG-DL-PA-L-PA) with gradient flexibility in water. Aqueous solutions of PEG-L-PA-DL-PA underwent only sol-to-gel transition, whereas those of PEG-DL-PA-L-PA underwent sol-to-gel-to-squeezed gel transitions as the temperature increased. The L-PAs of both polymers have an a-helical secondary structure in water at low temperature. However, the alpha-helical structure of the PEG-DL-PA-L-PA changed into a random coil structure as the temperature increased above 40 degrees C, whereas the PEG-L-PA-DL-PA kept the alpha-helical secondary structure over the same investigated temperature range of 4 degrees C to 50 degrees C. Cryo-transmission electron microscopy images and dynamic light scattering suggested that the PEG-L-PA-DL-PA develops spherical micelles, whereas the PEG-DL-PA-L-PA develops cylindrical bundles as well as spherical micelles in water. Even though both block copolymers have a similar composition of (ethylene glycol)(44), (L-alanine)(9), and (DL-alanine)(9), they showed significantly different temperature-sensitivities as well as different nano-assemblies in water. This report suggests that the block sequence of a polymer is very important in developing a specific nano-structure as well as in controlling thermosensitivity of the polymer, thus providing useful molecular information in designing a biomaterial.