Physiologically Crowded Artificial Cells for Relevant Drug Screens
High-throughput drug screening is critical to drug development. It relies on automated testing of thousands of chemical or biological compounds for their interactions with biological targets. However, the dilute buffer environment is quite different from the crowded in vivo intracellular compartment in which many, many molecules are moving around and interacting in a very small space. A candidate that performs well in a drug screen may not do so in a living cell where its motion and activity will be impeded by many obstacles generating all sorts of forces at relatively short range. The EU-funded PArtCell project is creating artificial cells that mimic weak non-specific interactions. This unique preparation will rely on a matrix developed on the basis of data obtained using engineered fluorescent probes to measure the interactions in healthy and stressed living cells. PArtCell will not only shine light on this ‘dark matter of biology’ but also enable screening of therapeutic targets under conditions mimicking nature.