Tandem-repeat proteins introduce tuneable properties to engineered biomolecular condensates

The ability of the cell to rapidly partition biomolecules into biomolecular condensates has been linked to a diverse range of cellular functions. To understand how the structural and dynamic attributes of these biomolecular condensates are linked with their biological roles, it is important to develop synthetic systems that allow systematic tuning of their physicochemical properties. Here, we describe the design and characterisation of a phase-separating consensus-designed tetratricopeptide repeat (CTPR) protein platform to make precise and predictable changes that both tune the condensate propensity and endow the condensates with new functions. We show that by incorporating short binding motifs into the CTPR domain we can specifically recruit target proteins to the dense phase of the condensate. The extent of target recruitment correlates with the binding affinity of the motifs. The relationship between CTPR domain modulation and condensate propensity observed experimentally is recapitulated by in silico modelling, giving us the ability to apply in silico methods to rationally design novel functional biomolecular condensates. ### Competing Interest Statement The authors have declared no competing interest.