Molecular self-assembly is a versatile bottom-up approach that allows the development of
nanostructures with unique properties.[1, 2] Such structures can be specifically designed to mimic
the dynamics of natural biosystems by incorporating bioactive stimuli-responsive units.[3] Until now,
self-assembling bioapproaches have used mainly bioactive peptide amphiphiles (PA) of different
complexity as proteins analogues. However, in the pericellular space, most of the proteins are
decorated with carbohydrates by a process called glycosylation. This process is used by Nature to
diversify the proteins’ roles by instructing their folding and by creating specific scripts readable in
recognition events and activating different signalling pathways. So far, these carbohydrates
bioactivites are overlooked in the design of molecular self-assembling blocks for the synthesis of
biofunctional supramolecular gels. Herein, we propose a simple strategy for introducing
carbohydrate moieties as components of supramolecular gels - co-assembly of simple carbohydrate
and peptide amphiphiles. These materials combine the simplicity of small molecules with the
versatility of glycans and proteins, respectively. We demonstrate that the co-assembly of these
amphiphiles occurs in aqueous environment and that the obtained assemblies have properties that
differ from the structures generated by the individual components. The co-assembled nanofibrils are
longer, branched and have different mechanical properties. These differences depend on the used
carbohydrate. We also show that the obtained nanofibrils form supramolecular hydrogels under
physiological conditions (e.g. in cell culture medium). The properties of these macroscopic hydrogels
can be tuned by functionalization of the carbohydrate: enzyme-responsive biomaterials or reservoirs
for protein delivery are two of the biomedical applications that we demonstrate.