Functional and Morphological Adaptation in DNA Protocells via Signal-Processing Prompted by Artificial Metalloenzymes

For life to emerge, confinement of catalytic reactions within protocellular environments has been proposed as a decisive aspect to regulate chemical activity in space.(1) Today, cells and organisms adapt to signals(2–6) by processing them through reaction networks that ultimately provide downstream functional responses and structural morphogenesis.(7,8) Re-enacting such signal processing in de-novo designed protocells is a profound challenge, but of high importance for understanding the design of adaptive systems with life-like traits. We report on engineered all-DNA protocells(9) harbouring an artificial metalloenzyme(10) whose olefin metathesis activity leads to downstream morphogenetic protocellular responses with varying levels of complexity. The artificial metalloenzyme catalyses the uncaging of a pro-fluorescent signal molecule, that generates a self-reporting fluorescent metabolite designed to weaken DNA duplex interactions. This leads to pronounced growth, intra-particular functional adaptation in the presence of a fluorescent DNA mechanosensor,(11) or inter-particle protocell fusion. Such processes mimic chemically transduced processes found in cell adaptation and cell-to-cell adhesion. Our concept showcases new opportunities to study life-like behaviour via abiotic bioorthogonal chemical and mechanical transformations in synthetic protocells. Furthermore, it reveals a strategy for inducing complex behaviour in adaptive- and communicating soft-matter microsystems, and illustrates how dynamic properties can be upregulated and sustained in micro-compartmentalized media.