Designing Complex Micellar Structures through Synergistic Physical Phenomena

Peptide amphiphiles (PAs) are a class of diblock biomaterials made of hydrophilic peptide head(s) conjugated to hydrophobic lipid tail(s) that self-assemble into peptide amphiphile micelles (PAMs) in water. Due to their unique properties, these nanomaterials are useful for a variety of applications ranging from process engineering to biomedical engineering. After two decades of research, the fundamental thermodynamic principles that govern micelle formation are well understood. In specific, critical packing parameter is an excellent tool researchers can utilize to control basic PAM structure making the design of first-order micellar structures such as spheres, cylinders, bi-layers, and inverse micelles quite straightforward. In recent years, second-order micellar structures like twisted ribbons and helices have been discovered which are believed to be formed due to unevenly distributed hydrogen bonds within the micelles. While exciting, tailorability of the shape and the responsiveness of complex micelles has not yet been achieved limiting their application for more complicated engineering problems. We hypothesized that by introducing a secondary physical phenomenon (i.e. electrostatic interactions) on top of hydrophobically-driven self-assembly we could create a novel set of PAs that would form unique micellar structures that are stimuli responsive. To probe this hypothesis, we synthesized a class of triblock PAs that possess a moderately hydrophilic peptide region, a zwitterionic peptide region, and hydrophobic tail(s). These zwitterionic-containing triblock PAs can undergo electrostatic complexation between PAs within a micelle and across micelles potentially allowing for micelles to associate with one another. Depending on the number of tails and location of zwitterionic peptide region, different complex shapes were formed including cylindrical micelles that twined together before further braiding into a third-order micellar structure that has not been previously reported in the literature. In addition to their exotic morphology, these “braided micelles” were found to be quite stable when exposed to certain environmental conditions like the presence of proteins and liposomes but partially disassociated into lower order micelles due to pH changes. These results have helped us to begin to understand the physical phenomena that govern higher-order micellar structures and start to generate design rules which will serve as a toolbox that can be leveraged for a wide variety of engineering applications.