Stable micelles based on a mixture of coiled-coils: the role of different oligomeric states

Homomeric micelles with tunable size, shape and stability have been extensively studied for biomedical applications such as drug carriers. However, designing the local valency and self-assembled morphology of nanophase-separated multicomponent micelles with varied ligand binding possibilities remains challenging. Here, we present micelles self-assembled from amphiphilic peptide-PEG-lipid hybrid conjugates, where the peptides can be either a 3-helix or 4-helix coiled-coil. We demonstrate that the micelle size and sphericity can be controlled based on the coiled-coil oligomeric state. Using theory and coarse-grained dissipative particle dynamics (DPD) simulations in an explicit solvent simulation, we studied the distribution of 3-helix and 4-helix conjugates within the mixed micelles and observed self-organization into nanodomains within the mixed micelle. We discovered that the phase separation behavior is dictated by the geometry mismatch in the alkyl chain length from different coiled-coil oligomeric states. Our analyses of the self-assembly tendency and drug delivery potency of mixed micelles with controlled multivalency provide important insights into the assembly and formation of nanophase-separated micelles.