Supercharged Proteins and Polypeptides

Abstract Electrostatic interactions play a vital role in nature. Biomacromolecules such as proteins are orchestrated by electrostatics, among other intermolecular forces, to assemble and organize biochemistry. Natural proteins with a high net charge exist in a folded state or are unstructured and can be an inspiration for scientists to artificially supercharge other protein entities. Recent findings show that supercharging proteins allows for control of their properties such as temperature resistance and catalytic activity. One elegant method to transfer the favorable properties of supercharged proteins to other proteins is the fabrication of fusions. Genetically engineered, supercharged unstructured polypeptides (SUPs) are just one promising fusion tool. SUPs can also be complexed with artificial entities to yield thermotropic and lyotropic liquid crystals and liquids. These architectures represent novel bulk materials that are sensitive to external stimuli. Interestingly, SUPs undergo fluid–fluid phase separation to form coacervates. These coacervates can even be directly generated in living cells or can be combined with dissipative fiber assemblies that induce life‐like features. Supercharged proteins and SUPs are developed into exciting classes of materials. Their synthesis, structures, and properties are summarized. Moreover, potential applications are highlighted and challenges are discussed.