Self‐assembled structures obtained from organic molecules have shown great potential for applications in a wide range of domains. In this context, short peptides prove to be a particularly versatile class of organic building blocks for self‐assembled materials. These species afford the biocompatibility and polymorphic richness typical of proteins while allowing synthetic availability and robustness typical of smaller molecules. At the nano‐to‐mesoscale, the architectures obtained from peptide units exhibit stability and a large variety of morphologies, the most common of which are nanotubes, nanoribbons, and nanowires. This review describes the formation of peptide‐based self‐assembled structures triggered by different stimuli (e.g., ionic strength, pH, and polarity), and the interactions that drive the assembling processes. It is surveyed how judicious molecular design is exploited to impart favourable assembling properties to afford systems with desired characteristics. A large body of literature provides the experimental and in silico data to predict self‐assembly in a given peptide system and obtain different supramolecular organizations for applications in a wide range of fields, from transport to sensing, from catalysis to drug delivery and tissue regeneration.

The spontaneous assembly of a peptide bolaamphiphile in water, namely, RFL₄FR (R, arginine; F, phenylalanine; L, leucine) is investigated, along with its novel properties in surface modification and usage as substrates for cell culture. RFL₄FR self-assembles into nanosheets through lateral association of the peptide backbone. The L₄ sequence is located within the core of the nanosheets, whereas the R moieties are exposed to the water at the surface of the nanosheets. Kinetic assays indicate that the self-assembly is driven by a remarkable two-step process, where a nucleation phase is followed by fast growth of nanosheets with an autocatalysis process. The internal structure of the nanosheets is formed from ultrathin bolaamphiphile monolayers with a crystalline orthorhombic symmetry with cross-β organization. We show that human corneal stromal fibroblast (hCSF) cells can grow on polystyrene films coated with films dried from RFL₄FR solutions. For the first time, this type of amphiphilic peptide is used as a substrate to modulate the wettability of solid surfaces for cell culture applications.