Spontaneous Transition of Self-assembled Hydrogel Fibrils into Crystalline Microtubes Enables a Rational Strategy To Stabilize the Hydrogel State

Hydrogel fibril and crystal formation are related self-assembly processes that provide materials with distinct emergent properties. The relationship between fibril and crystal growth is poorly understood, and efforts to engineer controlled hydrogelation vs crystallization via small molecule self-assembly currently depend on empirical approaches. Herein, we report the dynamic transition of self-assembled hydrogel fibrils of a phenylalanine (Phe) derivative, Fmoc-p-nitrophenylalanine (Fmoc-4-NO2-Phe), to crystalline microtubes. As has been shown with other Fmoc-Phe derivatives, Fmoc-4-NO2-Phe spontaneously self-assembles into amyloid-like fibrils that form an entangled hydrogel network when suspended in water. However, Fmoc-4-NO2-Phe fibrils uniquely transform over time into crystalline microtubes. Hydrogel fibrils appear to be a kinetic state with microtube crystals more thermodynamically favored. This dynamic transition from fibril to crystal has enabled a high-resolution structural analysis of the packing orientation of these self-assembled materials. Taking cues from this structural analysis, we demonstrate a rational strategy for stabilization of the kinetic Fmoc-4-NO2-Phe hydrogel fibrils. These results represent significant advances in our understanding of the dynamic nature of self-assembly processes and in our ability to rationally engineer these processes to provide materials with desired emergent properties.