Force-responsive nanoreactors inspired by glowing plankton

As night falls on certain beaches around the world, the sea can glitter like stars in the sky. This ‘sea sparkle’ arises from single-celled organisms that have evolved to emit light at night when disturbed by movements such as a wave breaking or a fish swimming by. This natural phenomenon inspired NCCR Bio-Inspired Materials researchers to create polymer-based nanoreactors that can be switched on by shear stress, allowing the activation of chemical reactions on demand. The nanoreactors could be used for drug delivery, 3D printing and scratch-and-smell items, among other applications.

In the plankton Noctiluca scintillans, mechanical stimulation generates an action potential that activates proton channels in the membrane of organelles called scintillons, changing their permeability. The influx of protons then triggers a chemical reaction that produces light. NCCR Principal Investigator (PI)  Prof. Nico Bruns - now at the Technical University of Darmstadt in Germany - and his colleagues set out develop mimics of scintillons made of synthetic polymers called polymersomes. “We didn’t invent polymersomes, but we asked ourselves, can we switch the permeability of polymersomes by mechanical perturbation?” Bruns says.

To create such force-responsive polymersomes, the researchers turned to a second source of inspiration: DNA. The inside of the DNA double helix repels water; but when the nucleobases that join two DNA strands together unpair, the whole molecule becomes water-soluble.

Bruns and his colleagues created vesicles in which a fluid is enclosed by an outer, double-layered membrane. The membrane consists of heads made of water-loving polymer chains and tails made of water-repellent polymer chains that are linked to nucleobases. The nucleobases cluster together when paired, but after applying shear force to the vesicles, for example by aspirating them with a syringe, the nucleobases unpair, making the membrane permeable to water-soluble molecules.

Next, the team enclosed in the vesicles an enzyme that produces light and provided the substrate on the outside. “If the membrane is non-permeable for the substrate, nothing will happen, but when the membrane becomes permeable, then substrate can get into the vesicle and the enzyme can do its job,” Bruns says. Indeed, in response to shear force, the polymersomes light up — like tiny glowing Noctiluca scintillans, the researchers found. “It was nice to show that we could mimic the biological role model,” Bruns says.

Finally, the team used shear-responsive polymersomes to trigger a chemical reaction that transforms polymers into a gel. In this case, the force generated by mild ultrasound was enough to make the nanoreactors permeable and switch on the gelation reaction. Gel formation on demand could be used in biomedicine to create hydrogel patches that gradually release drugs. It could also be useful in 3D printing to turn liquid inks into gels only after the ink is squeezed through a nozzle.

Another possible application of polymer nanoreactors could be in scratch-and-smell items. “One could use mechanical perturbations — for example, rubbing a garment — to release a fragrance,” Bruns says.

The researchers detailed the structure and the properties of the polymer nanoreactors in the journal Angewandte Chemie International Edition. The work stems from a collaborative effort between the research teams of Bruns, and NCCR Bio-Inspired Materials PIs Prof. Esther Amstad (EPFL) and Prof. Marco Lattuada (University of Fribourg). Lattuada brought fluid dynamics expertise to the project, while Amstad and her team provided a sophisticated experimental setup to prove that nanoreactors are activated by shear force, Bruns says.

The work, he adds, showcases the highly collaborative nature of the NCCR Bio-Inspired Materials. “The NCCR allowed us to collaborate with Marco, Esther and their groups with a very low level of activation energy,” he says. “This merging of expertise is key for highly interdisciplinary research.”

Reference: Rifaie-Graham, O.; Galensowske, N. F. B.; Dean, C.; Pollard, J.; Balog, S.; Gouveia, M. G.; Chami, M.; Vian, A.; Amstad, E.; Lattuada, M.; Bruns, N. Shear stress‐responsive polymersome nanoreactors inspired by the marine bioluminescence of dinoflagellates, Angew. Chem. Int. Ed., 2020, 60, 904-909.

Text by Giorgia Guglielmi