Designing Pathway-Controlled Multicomponent Ultrashort Peptide Hydrogels with Diverse Functionalities at the Nanoscale for Directing Cellular Behavior.

Tuning self-assembling pathways by implementing different external stimuli has been extensively studied, owing to their effective control over structural and mechanical properties. Consequently, multicomponent peptide hydrogels with high structural tunability and stimuli responsiveness are crucial in dictating cellular behavior. Herein, we have implemented both coassembly approach and pathway-dependent self-assembly to design nonequilibrium nanostructures to understand the thermodynamic and kinetic aspects of peptide self-assembly toward controlling cellular response. Our system involved an ultrashort peptide gelator and a hydrophilic surfactant which coassembled through different pathways, i.e., heat-cool and sonication methods with variable energy input. Interestingly, it was possible to access diverse structural and mechanical properties at the nanoscale in a single coassembled system. Further, the hydrophilic surfactant provided additional surface functionalities, thus creating an efficient hydrophilic matrix for cellular interaction. Such diverse functionalities in a single coassembled system could lead to the development of advanced scaffolds, with applications in various biomedical fields.