Autonomous chemo-metabolic construction of anisotropic cell-in-shell nanobiohybrids in enzyme-powered cell...

Living organisms use intricate strategies to adapt and survive in response to potentially lethal environment changes. Inspired by cryptobiosis in nature, researchers have pioneered approaches to create cell-in-shell nanobiohybrids, aiming to endow cells with enhanced protection and exogenous functions. Yet, these methods still lack the biological autonomy intrinsic to natural cellular responses. Here, we present an innovative chemo-metabolically coupled strategy for the autonomous construction of cell-in-shell structures in cell growth medium. Our system harnesses ethanol fermentation by Saccharomyces cerevisiae, chemically coupled with an enzymatic cascade involving alcohol oxidase and horseradish peroxidase, to drive the nanoshell formation of polydopamine. The integration of autonomous shell formation with cellular proliferation produces anisotropic cell-in-shell structures, which can serve as enzyme-powered cell microrobots, upon conjugation with urease. Our autonomous system enables the creation of cell-in-shell nanobiohybrids with dynamic and adaptive environmental interactions, paving the way for transformative applications in synthetic biology, such as artificial cells, as well as advancements in cell-based therapies.