Delivery of peptide coacervates to form stable interaction hubs in cells

Cells contain membrane-bound and membraneless organelles that operate as spatially distinct biochemical niches. However, these reaction centers lose fidelity due to aging or diseases. A grand challenge for biomedicine is restoring or augmenting cellular functionalities. An excited strategy is the delivery of protein-based materials that can directly interact with cellular biological networks. In this study, we sought to develop long-lasting materials capable of cellular uptake, akin to intracellular interaction hubs. We develop a delivery method to efficiently transplant stable micron-size peptide-based compartments into living cells. By loading coacervates with nanobodies and bioPROTACs, we demonstrate successful target sequestration of natively expressed GFP to our synthetic hubs, and function as bioreactors to selectively degrade GFP inside human cells. These results represent an important step toward the development of synthetic organelles that can be fabricated in vitro and taken up by cells for applications in cell engineering and regenerative medicine. Short HBpep peptides assemble into micron-size coacervates that are efficiently taken up by various cell types and stably retained for days. Nanobodies and bioPROTACs loaded in the coacervates enable interaction with native targets and these hubs can function as a bioreactor for target degradation