3 years ago

Sub-20 nm Stable Micelles Based on a Mixture of Coiled-Coils: A Platform for Controlled Ligand Presentation

Sub-20 nm Stable Micelles Based on a Mixture of Coiled-Coils: A Platform for Controlled Ligand Presentation
Sinan Keten, Benson T. Jung, Ting Xu, JooChuan Ang, Dan Ma
Ligand-functionalized, multivalent nanoparticles have been extensively studied for biomedical applications from imaging agents to drug delivery vehicles. However, the ligand cluster size is usually heterogeneous and the local valency is ill-defined. Here, we present a mixed micelle platform hierarchically self-assembled from a mixture of two amphiphilic 3-helix and 4-helix peptide-polyethylene glycol (PEG)-lipid hybrid conjugates. We demonstrate that the local multivalent ligand cluster size on the micelle surface can be controlled based on the coiled-coil oligomeric state. The oligomeric states of mixed peptide bundles were found to be in their individual native states. Similarly, mixed micelles indicate the orthogonal self-association of coiled-coil amphiphiles. Using differential scanning calorimetry, fluorescence recovery spectroscopy, and coarse-grained molecular dynamics simulation, we studied the distribution of coiled-coil bundles within the mixed micelles and observed migration of coiled-coils into nanodomains within the sub-20 nm mixed micelle. This report provides important insights into the assembly and formation of nanophase-separated micelles with precise control over the local multivalent state of ligands on the micelle surface.

Publisher URL: http://dx.doi.org/10.1021/acs.biomac.7b00917

DOI: 10.1021/acs.biomac.7b00917

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