Polymer Assembly Mediated by Attractive Crowding Agents: Good-Solvent vs Poor-Solvent Polymers

Abstract Polymer assembly dictates the functional performance of soft materials and is fundamentally associated with intracellular liquid–liquid phase separation (LLPS), a ubiquitous process in living cells. Macromolecular crowding exerts dramatic regulatory effects on both assembly dynamics and condensate morphologies. Although extensive studies concerning macromolecular crowding effects have long focused on repulsive interactions, a systematic mechanistic picture describing how attractive crowders tune the structural and dynamic features of polymer assemblies and LLPS remains elusive. Herein, we construct a coarse-grained Langevin model to simulate polymer-crowder aggregation of good-solvent and poor-solvent chains by adjusting intercrowder attraction, crowder size and crowder concentration. Our results demonstrate a series of novel structural and kinetic features. Intercrowder interaction strength serves as a key switch governing condensate morphology: good-solvent polymers evolve sequentially from crowder-bridged clusters to homogeneous mixed droplets and core–shell assemblies, whereas poor-solvent chains form compact self-aggregates, cage-confined multiclusters or patchy core–shell structures. Crowders with large sizes impose dominant geometric packing restrictions, generating distinctive porous and layered condensates. Increasing crowder concentration can fully dissociate good-solvent polymer aggregates while merely breaking poor-solvent polymer clusters into small separated domains. Moreover, a prevailing three-step assembly mechanism involving nucleation, diffusion-limited lag and cluster coalescence is identified for all polymer systems. This work establishes an integrated framework interpreting the competition between crowding-mediated bridging and intrinsic assembly of poor-solvent polymers. The new insights yielded in this study enrich our understanding of intracellular condensates and provide useful guidance for functional polymer design.