Programming complex pathway-driven self-assemblies in a minimal supramolecular biopolymer model

Living systems self-assemble into dynamic supramolecular structures through complex pathways, enabling distinct functions. This is because natural processes rely on kinetic pathways rather than thermodynamic stability, keeping systems in an out-of-equilibrium state and enabling diverse functional outcomes from the same set of monomers. Replicating this pathway complexity in artificial systems remains challenging. Here, we report a minimal supramolecular model that exhibits programmable, pathway-dependent structural evolution into distinct states, including phase-separated droplets, metastable hydrogels, kinetically trapped hydrogels, and thermodynamically stable crystals. The system undergoes a spontaneous transition from initially forming droplets to nanofibrils via liquid-liquid and liquid-solid phase separation, leading to a sol-gel transition, followed by a gel-to-crystal transition in a binary solvent system. By modulating the solvent composition and pH, the assembly pathway can be directed to yield structurally distinct polymorphs with properties different from the equilibrium state. The dynamics of structural transformation can be finely tuned to entrap the metastable droplets or hydrogels or bypass the intermediate gel state altogether to directly form crystalline assemblies. Moreover, the lifetime of transient hydrogels can be programmed by modulating the nature of self-assembly, making dynamic hydrogels suitable for applications such as controlled release. These results offer a simple strategy to regulate the pathway complexity and obtain diverse functional materials.