In natural cells, adaptive behavior is orchestrated by internal sensing-actuation mechanisms that dictate the dynamic switching of biological structures. In general, these adaptive mechanisms are based on processing certain internal or external molecular cues into internal changes that ultimately govern the status of the cell. It is well known that cells adapt their viscosity, metabolic status, and growth according to the energy and the number (concentration) of signaling molecules (e.g., hormones) available. Notwithstanding, replicating such cellular adaptability and implementing generic strategies for dynamic adaptive behavior in artificial cells remains still very challenging. In previous research, our group presented a strategy to spatially organize protein fragments inside GLVs through pH-reversible interactions with the membrane, inducing a biochemical response. Indeed, research into the design of artificial cells able to dynamically respond to external stimulus resulting in adaptive behavior is still very limited – in part, progress is hampered by the lack of versatile strategies for integrating structural responsive elements and self-regulation pathways in one artificial compartment.<br/>In this lecture we will present the design of dynamic stimuli-responsive artificial cells based on the direct integration of a supramolecular pH-responsive hydrogel in phospholipid compartments, resulting in giant hydrogel in lipid vesicles (GHiLVs) as a novel platform. In particular, the encapsulated hydrogel consists of poly(ethylene glycol) functionalized with ureido-pyrimidinone (UPy) moieties, which form four-fold hydrogen bonds enabling dimerization between polymeric chains. Our results indicate that the resulting GHiLV artificial cells are capable of dynamic viscoadaptation, showing adaptive regulation of its internal viscosity according to the pH of the medium, i.e., with a low viscosity at basic pH and with high viscosity at acidic pH. In addition, we show that regulatory enzymatic machinery can be incorporated in the system, yielding GHiLVs adaptive to the presence of molecular cues. Finally, we demonstrate that GHiLV viscoadaptation enables modulation of its metabolic activity, which opens new possibilities for the design of adaptive cell-like microreactors.

Giant hydrogel in lipid vesicles as dynamic stimuli-responsive artificial cells

ACS Spring 2022

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