Receptor-Mediated Transmembrane Activation of Protein Folding in Synthetic Cells

Synthetic cells are a rapidly maturing platform with emerging applications in biomedicine and biotechnology. The specific novelty of this work is that we develop synthetic cells that respond to an extracellular stimulus by performing the folding of an encapsulated polypeptide into a functional enzyme. To this end, we developed artificial transmembrane signaling receptors. These contain an extracellular enzyme-responsive group, a self-immolative linker as the mechanism of signal transduction, and a secondary messenger molecule with intracellular activity. The secondary messenger is chosen such that it initiates protein refolding from the denatured polypeptide. Results of this study expand the molecular toolbox for the design of synthetic cells with life-like, responsive behavior.