Super-resolution imaging guides the design of biocompatible microswimmers

Two IBEC groups have clubbed together to combine their expertise and reveal new knowledge that could advance the design of micro- and nanomotors for applications in health.

By harnessing the unprecedented resolution of Lorenzo Albertazzi’s group’s STORM microscope, Samuel Sánchez’s group – in collaboration with Erik Schäffer’s group at the University of Tübingen – have been able to reveal new information about how their enzyme-powered nanomotors achieve motion.

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Left: a conventional fluorescence analysis of the silicon dioxide-coated micromotors functionalized with urease compared with STORM imaging of the same; right, a 3D density map obtained by computational analysis of STORM imaging

Motors that use enzyme catalysis to self-propel are some of Samuel’s Smart Nano-Bio-Devices group’s most promising nanomachines, as they offer more biocompatibility and versatility than others that use traditional toxic fuels such as hydrogen peroxide, and thus offer potential as safe capsules for targeted drug delivery. The group’s recent research has achieved self-propelling nanomotors powered by enzymes such as urease or glucose oxidase, but nevertheless, the key parameters that underlie the motion achieved by these enzyme-powered machines are still not completely understood.

By working together with Lorenzo’s Nanoscopy for Nanomedicine group, who are experts in STORM, a super-resolution imaging method that goes beyond the resolution of conventional light microscopy, Samuel’s group was able to investigate the role that enzyme distribution and quantity plays in generating active motion.

“STORM allowed us to do a 3D mapping of urease enzymes bound to the surface of micromotors at single-molecule resolution,” says Tania Patiño, a postdoc in the Smart Nano-Bio-Devices group and first author of the paper. “We looked at two types of nanomotors – one made with polystyrene and the other with polystyrene coated with a rough silicon dioxide shell.”

The researchers had seen that the second type of motors had a faster directional propulsion compared to their polystyrene-only counterparts. Using STORM, they were able to detect single molecules of the fuel – the enzyme urease – on the micromotors’ surfaces and see what differences or variations might be contributing to the differences in speed.

“Both types of motors had an asymmetric distribution of enzymes around their surfaces, so we knew it wasn’t only their distribution that was affecting the different motion behavior,” says IBEC group leader and ICREA research professor Samuel, who directed the research. “However, when we counted the urease molecules – which we were only able to do thanks to STORM – we saw that there was a 10-fold increase in number of enzymes on the silicon dioxide-shelled nanomotors compared to the polystyrene-only ones; in other words, rough surfaces allow a higher enzyme binding, leading to active motion.”

To further understand the role of enzyme number in self-propulsion of micromotors, the researchers correlated the number of enzymes, quantified by STORM, with the speed and propulsive force, finding a specific threshold of number of molecules for the motors to swim. “These results provide new insights into the design features of micro- and nanomotors, and will help us in achieving cargo transporters that can be used safely and in a targeted, efficient manner in the body,” says Samuel.

Tania Patiño, Natalia Feiner-Gracia, Xavier Arqué, Albert Miguel-López, Anita Jannasch, Tom Stumpp, Erik Schäffer, Lorenzo Albertazzi, Samuel Sánchez (2018). Influence of enzyme quantity and distribution on the self-propulsion of non-Janus urease powered micromotors. J. Am. Chem. Soc., epub ahead of print