Programmable Zwitterionic Droplets As Biomolecular Sorters and Model of Membraneless Organelles

It is emerging that cells can regulate biochemical functions by generating open compartments with well-defined composition. One important mechanism underlying this control is simple coacervation driven by disordered proteins that encode multivalent interactions. Inspired by these observations, here we develop programmable droplets based on simple coacervation of synthetic responsive polymers that mimic the architecture of these biological disordered proteins. We have adopted a bottom-up approach starting from zwitterionic polymers, demonstrating that they can form liquid droplets that exclude most molecules. Starting from this reference material we have progressively introduced in the polymer architecture an increasing number of different intermolecular interactions. With this strategy, we can independently control multiple properties of the droplets, such as stimulus responsiveness, polarity, selective uptake of client molecules and miscibility. We demonstrate that these droplets can separate and enable the detection of target molecules even within complex mixtures, opening attractive applications in bioseparation and in diagnostics.