Short-peptide amyloid assembly and disassembly play crucial roles in various research fields, which range from addressing pathologies that lack therapeutic solutions to the development of innovative soft (bio)materials. Hydrogels from short peptides typically show thermo-reversible gel-to-sol transition, whereby fibrils disassemble upon heating, and re-assemble upon cooling down to room temperature (rt). Despite ongoing intense research studies in this area, the majority focus on peptide-peptide interaction and neglect the structuring role of water in peptide supramolecular behavior. This study describes an unprotected tetrapeptide gelator that forms highly stable fibrils which, upon heating, re-organize into plates that persist upon cooling to rt. All-atom molecular dynamics (MD) simulations and experimental methods reveal water as a key player in the thermodynamics that accompany this irreversible morphological transition, and advance our understanding of supramolecular structures.
