LLPS-Driven Kinetic Trapping and Thermally Induced Structural Maturation in an Amyloid-Inspired Dipeptide Gel

Peptide nanoarchitectonics represents the controlled orchestration of dynamic and adaptive bioinspired organized nanostructures for versatile applications. Herein, we investigate the organization of an amyloid-inspired minimalistic dipeptide into diverse nanoarchitectonics. The dipeptide assembled via liquid-liquid phase separation into a kinetically trapped gel state, characterized by the coexistence of gel-like droplets and fibrous domains. This arrested state, upon heating, reached a thermodynamically stable organization with a dense network of thicker fibrils exhibiting improved mechanical properties and increased turbidity. This "thermal bisignate" gel-gel transition depended on the solvent composition; increased DMSO% led to thermoreversible gels showing a gel-sol-gel transition. This hierarchical evolution, spanning droplets and fibrils, exemplifies thermally programmable peptide nanoarchitectonics, offering new avenues to develop amyloid-inspired biomaterials with tunable properties.