Enzymes that move their substrate around could find applications in drug delivery and defence

Microscopic, non-mechanical pumps that are activated and powered by the fluids they move have been developed by researchers from the US, Russia and Puerto Rico. The micropumps work by converting chemical energy into movement and have a variety of potential applications, from breaking down nerve agents to automatic insulin delivery in response to glucose.

‘The non-mechanical, self-powered nano/micro-scale pumps precisely control flow rate and turn on in response to specific stimuli,’ explains Ayusman Sen, who led the research at Pennsylvania State University, US.

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The enzymes act as microscopic pumps, transporting the substrate fluid

The pumps are formed from enzymes tethered to a patterned gold surface. In the presence of a given fluid substrate, the catalytic action of the enzymes converts chemical energy into motion, pumping the fluid in a directed manner without the need for an external power source. The researchers studied four different enzymes – catalase, glucose oxidase, lipase and urease – observing that the pumping velocity increased with higher concentrations of the target substrate. The pumps have a long shelf life, with the enzymes remaining viable even after prolonged storage.

While biological motors and pumps are powered by enzymes that convert adenosine triphosphate [ATP] into adenosine diphosphate, this study demonstrates that other mechanisms can work. ‘One need not be tied to this one specific reaction,’ says Sen, adding: ‘our results open up a new area of mechanobiology: intrinsic force generation by non ATP-dependent enzymes and their role in fluid transport in and outside biological systems.’

According to Sen, the pump design has the potential for use in a wide variety of applications. The principle can be adapted to create environmentally sensitive drug delivery devices, in which a positively charged hydrogel scaffold is used to both immobilise the enzymes and carry a cargo of small molecules, which can be released when the enzymes are triggered by a chosen substrate. As a proof-of-concept, the team developed a microdevice that can release insulin in response to the presence of glucose.

Another application is anticipated by the US Defense Threat Reduction Agency, whose partial funding of the research will support the development of pumps specifically designed to neutralise nerve agents and deliver appropriate antidotes. In a similar fashion, the team should be able to design devices triggered by the chemical signals of other biological agents, such as bacteria. They are also looking into creating pump assemblies, based on enzyme cascades, which could create flow networks that respond to specific substrates, inhibitors or activators.

Reynaldo Villalonga, a chemist at the Complutense University of Madrid in Spain, calls the micropumps ‘imaginative’, highlighting the devices’ potential for opening new research horizons in such diverse fields as biomedicine, biosensing, applied pharmacology and agriculture. He adds that the work could be ‘a cornerstone for the future design of enzyme-powered micro- and nanorobots, and their use as smart drug delivery systems, theragnostic agents and intelligent nanoscalpels for minimally invasive surgery’.