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.

中文翻译：

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基于螺旋线圈混合物的20纳米以下稳定胶束：可控配体表示的平台

配体官能化的多价纳米颗粒已被广泛研究用于从成像剂到药物输送载体的生物医学应用。但是，配体簇的大小通常是异质的，局部化合价是不确定的。在这里，我们介绍了从两个两亲的3螺旋和4螺旋肽-聚乙二醇（PEG）-脂质杂化共轭物的混合物分层自组装的混合胶束平台。我们证明胶束表面上的局部多价配体簇大小可以基于卷曲螺旋低聚状态来控制。发现混合的肽束的低聚状态为它们各自的天然状态。类似地，混合的胶束表明卷曲螺旋两亲物的正交自缔合。使用差示扫描量热法，荧光回收光谱法 以及粗粒分子动力学模拟，我们研究了混合胶束中卷曲螺旋束的分布，并观察了卷曲螺旋向20 nm以下混合胶束中纳米域的迁移。该报告提供了对纳米相分离的胶束的组装和形成的重要见解，可以精确控制胶束表面上配体的局部多价态。