The functioning of synthetic gene circuits depends on their local chemical context defined by the types and concentrations of biomolecules in the surrounding milieu that influences gene transcription and translation. This chemical-context dependence of synthetic gene circuits arises from significant yet unknown cross talk between engineered components, host cells, and environmental factors and has been a persistent challenge for synthetic biology. Here, we show that the sensitivity of synthetic gene networks to their extracellular chemical contexts can be minimized, and their designed functions rendered robust using artificial cells, which are synthetic biomolecular compartments engineered from the bottom-up using liposomes that encapsulate the gene networks. Our artificial cells detect, interact with, and kill bacteria in simulated external environments with different chemical complexity. Our work enables the engineering of synthetic gene networks with minimal dependency on their extracellular chemical context and creates a new frontier in controlling robustness of synthetic biological systems using bioinspired mechanisms.

Advances in materials engineering have allowed for the development of sophisticated and controlled drug delivery through vesicles. Smart vesicles, capable of sensing single stimulus or multiple stimuli, can be engineered to process specific environmental signals to produce a tailored response. Exhibiting multifunctionality and theranostic abilities, they are a promising platform for new therapeutic methods. Here, we discuss smartness in the context of biosensing vesicles, followed by the various components required to develop a smart vesicle and the design considerations regarding engineering approaches of each. We then focus on biomedical applications of the vesicles in disease treatment and biosensing.