Development of DNA nanotechnology for chemotactic artificial cells

One of the core aims of bottom-up synthetic-biology to produce artificial cells: constructs prepared from elementary molecular components that mimic one or more functionalities of biological cells. Owing to the complete programmability of their behaviour and composition, these cell mimics have widespread promise in areas such as drug delivery, biochemical synthesis, and biosensing. Importantly, artificial cells have the potential to be used for the in-vivo production and release of therapeutic agents in response to disease-related molecular stimuli. A key ability that artificial cells should have in this context is that of targeting diseased cells or tissue, in order to reduce the toxicity of the treatment. Short-range targeting can be achieved by functionalising the surface of artificial cells with ligands that specifically bind receptors overexpressed in diseased tissues. However, advances in DNA nanotechnology have meant an even more valuable strategy is on the horizon: long-range targeting, i.e. the ability to detect the presence of the target at a distance and move towards it. For such a response to be implemented, artificial cells require the ability to perform active motion, ideally along a chemical gradient (chemotaxis). This capability would be particularly desirable as chemical gradients often result from a high concentration of specific analytes in diseased areas, e.g. as part of the inflammatory response. In this project, we will combine DNA nanotechnology, microfluidics and theoretical modelling to develop general strategies to achieve motility in artificial cells. This technology has the potential to be used in a therapeutic context, for active motion of drug-delivery vehicles to their target site, as well as shedding light of fundamental cell biology through an 'understanding by building' approach.