Designer proteins could mean new treatments to tackle diseases with pinpoint accuracy, thanks to scientists who are developing miniscule machines to manipulate single molecules.
Researchers at the EU-funded MANAQA project in Switzerland are developing a system that can pick apart proteins, which are just a couple of nanometres in size.
While normal microscopes can be used to look at cells, proteins or molecules require tools like atomic force microscopes, which scan objects using a small probe called a cantilever.
The probe is dragged or tapped across an object line by line, almost like the needle on a record player. This data is then sent to a computer which can convert it into an image.
The MANAQA researchers have combined an atomic force microscope with a nanowire that allows scientists to manipulate molecules.
‘You can pull the nanowire magnetically to unfold the protein and the atomic force microscope cantilever will sense that,’ said Dr Salvador Pané who is coordinating the collaborative EU effort at the university ETH Zurich. ‘The advantage of that is with a nanowire you can, for example, pull objects, and depending on how you build it you can also apply torque.’
His team had to first design a nanowire that would work where protein samples thrive, mirroring the conditions of fluids in the body.
‘We can produce many nanostructures ... we know how to manipulate them. Now the further step is making them useful.’
Dr Salvador Pané, ETH Zurich
‘A system in which a protein exists is usually a very salty system, and an environment which has a lot of salt or electrolytes is a potential corrosion problem,’ said Dr Pané.
So far, researchers have found that using a nickel or cobalt-nickel alloy produces the best results. Those materials let the nanowire keep its magnetic properties but also hold up to briny conditions without deteriorating.
Scientists also needed to develop a computer model to predict how changing the magnetic field on the nanowire would alter its movement in a fluid, compensating for forces like drag.
While there are competing methods that can be used to trap nanoparticles, many have drawbacks. Trapping molecules with lasers, for instance, can end up overheating the material being tested. Using nanowires avoids that.
The team hopes by August this year to have demonstrated that the concept can allow proteins to be twisted and moved with greater range than ever before. That could eventually improve drug research, where one could unfold proteins in the presence of different substances to see where they reacted better.
‘I think now we are at the point in nanotechnology where we can produce many nanostructures, we know how to make them function, we know how to manipulate them. Now the further step is making them useful,’ Dr Pané said.
Manipulated molecules are also being used inside the body to treat disease. Scientists working on the EU-funded MRECB and DNA NANO-ROUTERS projects are folding strands of DNA to make so-called nanorobots that can be used to deliver drugs.
The advantage of DNA is that it can be folded into various shapes, a bit like making origami. A team at Israel’s Bar-Ilan University led by Dr Ido Bachelet and funded by the European Research Council is working on nanorobots that can be programmed to detect certain conditions, like a tumour, and then deliver drugs to treat the affected cells.
Taking that a step further, researchers on MRECB are trying to get the robots to behave as an intelligent swarm, for example linking together at the right point to help tissues regrow. The robots could even be used to alter the communication network between cells in the body by picking up and delivering signal molecules. That could stop cells from over-transmitting certain signals, such as an immune response.
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