This study describes the design and characterization of de novo protein hydrogels with programmable intra- and extracellular viscoelasticity. The authors used computational methods to design modular protein building blocks with controlled supramolecular interactions, valencies, geometries, and flexibility. These building blocks were then used to create hydrogels through covalent or noncovalent crosslinking, resulting in materials with a range of viscoelastic properties from fluids to gels. The rheological properties of the hydrogels were systematically investigated, showing that the stiffness and viscoelastic behavior could be tuned by varying the length of flexible linkers and rigid arms connecting the building blocks. The study also explored the cytocompatibility of these hydrogels, demonstrating their potential for 3D cell culture and tissue engineering applications. Additionally, the authors investigated the intracellular assembly of these protein networks, showing that they could form complex coacervates within living cells. The results highlight the potential of de novo protein design in creating tunable biomaterials with precise control over their mechanical properties, both in vitro and in vivo.This study describes the design and characterization of de novo protein hydrogels with programmable intra- and extracellular viscoelasticity. The authors used computational methods to design modular protein building blocks with controlled supramolecular interactions, valencies, geometries, and flexibility. These building blocks were then used to create hydrogels through covalent or noncovalent crosslinking, resulting in materials with a range of viscoelastic properties from fluids to gels. The rheological properties of the hydrogels were systematically investigated, showing that the stiffness and viscoelastic behavior could be tuned by varying the length of flexible linkers and rigid arms connecting the building blocks. The study also explored the cytocompatibility of these hydrogels, demonstrating their potential for 3D cell culture and tissue engineering applications. Additionally, the authors investigated the intracellular assembly of these protein networks, showing that they could form complex coacervates within living cells. The results highlight the potential of de novo protein design in creating tunable biomaterials with precise control over their mechanical properties, both in vitro and in vivo.