Revealing the Folding of Single-Chain Polymeric Nanoparticles at the Atomistic Scale by Combining Computational Modeling and X-ray Scattering

Predicting 3D structures of synthetic heterograft polymers in solution starting from a chemical structure remains a great challenge. Here, we get grip on the 3D structures formed by amphiphilic, random heterograft polymers in water depending on the nature of the hydrophilic graft. Atomistic MD simulations in explicit water on a μs time scale show that large Jeffamine-based grafts combined with randomly distributed hydrophobic grafts induce the formation of worm-like structures with local hydrophobic domains. Replacing Jeffamine by glucose affords core-shell ellipsoidal structures. The simulated small-angle X-ray scattering (SAXS) curves from the simulation results show excellent agreement with experimental SAXS results for the Jeffamine-based copolymers. For the glucose-based copolymers, the experimental SAXS results also indicated the presence of core-shell structures, albeit that (some) multichain aggregation was present. Our work highlights that global conformations of very large heterograft polymers (up to ∼30,000 atoms) can now be studied with (accelerated) MD simulations at the atomic scale in solvent (up to 2.5 million atoms). This joint approach constitutes a reliable tool to understand the folding and possible aggregation behavior of heterograft polymers in solution, paving the way toward predictive modeling of nanoparticle structures from a polymer’s chemical structure.