“…Biomolecules provide an almost limitless pool of evolutionary-optimized materials that can be exploited or repurposed to engineer materials with highly specialized functionalities. , Such materials include hydrogels: three-dimensional macroscopic networks swollen by large volumes of water, in some special cases up to 1000× its dry mass . Protein hydrogels use polypeptide chains as the hydrophilic network in order to exploit their intrinsic properties, ,− and they have found applications in tissue engineering, such as vascular grafts and neural tissue regeneration, as well as scaffolds for controlling cell behavior. − In addition, stimulus-responsive protein hydrogels have been explored as ligand-triggered actuators for biosensors and for controlled release for drug delivery. ,,− However, as most protein-based hydrogels are obtained from unstructured peptides or through aggregation of unfolded globular proteins, − the full spectrum of protein function (e.g., catalysis, signaling, and ligand binding) has not yet been exploited. A recent novel approach, that not only obviates these limitations but also harnesses their distinct functional properties, is to build hydrogels from tandem arrayed, folded globular proteins with known mechanical properties. ,, The mechanical properties of the native state of single, monodisperse proteins can be obtained by single molecule atomic force spectroscopy using the atomic force microscope (AFM) − or optical tweezers , as sensitive force transducers.…”