Temperature sensitive copolymers as a model system for understanding the physical basis of nonequilibrium assembly

Both natural biomaterials and synthetic materials benefit from complex energy landscapes that provide the foundation for structure-function relationships and environmental sensitivity. Understanding these nonequilibrium dynamics is important for the development of design principles to harness this behavior. Using a model system of poly(ethylene glycol) methacrylate-based lower critical solution temperature (LCST) copolymers, we explored the impact of composition, path, and macromolecular crowding effects on nonequilibrium thermal hysteretic behavior. Through turbidimetry analysis of non-superimposable heat-cool cycles, we observe that LCST copolymers show clear hysteresis that varies as a function of pendent side chain length and hydrophobicity. Hysteresis is further impacted by the temperature ramp rate, as insoluble states can be kinetically trapped under optimized temperature protocols. Finally, the use of common crowding agents shows that excluded volume effects diminish the hysteresis behavior. This systematic study brings to light practical design principles towards understanding and harnessing out-of-equilibrium effects in synthetic soft materials.