Hierarchical Shape-Specified Model Polymer Nanoparticles via Copolymer Sequence Control

Nature employs copolymer sequence to realize exquisite control of molecular shape in nanostructures such as protein assemblies, membranes, and DNA complexes. Synthesis of artificial sequence-controlled polymers has recently become viable, paving the way for synthetic materials mimicking biological nanostructures. Further advances are hindered by the poorly understood relationship between sequence and molecular shape. Here, we employ Brownian dynamics simulations to probe the relationship between the sequence of long copolymer chains and the resultant globular shapes realized in a selective solvent. Similar to prior work in multimolecular assembly of lower molecular weight chains, we find that sequence can mediate assembly into a range of single-molecule nanoparticulate shapes ranging from vesicles to sponges to necklaces. We find that, in single-molecule assembly, chain sequence can enable enhanced control of nanoparticulate dimensions, for example enabling simultaneous control of vesicle cavity and wall size. We additionally find that these assembled structures can be stabilized against aggregation via sequence incorporation of long solvophilic loops, and that sequence can be employed to place these loops preferentially on the outer leaflet of a vesicle. Finally, we show that combination of distinct sequence “motifs” into a single chain can yield more complex hierarchical structures. Combination of worm-coding and vesicle coding motifs into “motif diblocks”, for example, yields poreated vesicles and tubules in which pore size can be directly tuned by controlling the sequence of the worm-coding block. These results demonstrate the potential to utilizing an alphabet of synthetic motifs to enable access to single-molecule nanoglobular shapes relevant to applications including designer artificial enzymes, tubules, and confined catalysis sites.