Moving molecules

Ben Feringa is one of the pioneers in the world of molecular motors. He likes to tinker with motors, rotors and switches, but he does so at a molecular level. ‘Which makes it very difficult to see if your device actually works’, he remarks.

He presented the first molecular motor back in 1999. The molecule his team synthesized could perform a unidirectional 360-degrees rotation and was driven by light. One revolution took an hour. ‘Now, such a motor would make three million rotations per second’, says Feringa. ‘But that took some 50 new designs over ten years.’

Building molecular motors is not for the faint of heart. You can’t just get out your nuts and bolts and build one. These nanometer-sized molecules (one millionth of a millimetre) must be created step by step using chemical synthesis. Proving they actually work is equally difficult.

‘One thing we want to do with the new grant is to visualize the rotary movement’, Feringa explains. To do this, the one-nanometer motor is given a ten-nanometer extension with a a fluorescent dye attached to it. ‘We are working with one of the world’s leading experts in single-molecule visualization, Johan Hofkens from the University of Leuven.’

This type of visualization has been achieved with a natural motor, the ATPase enzyme. ‘But that’s a much bigger protein complex. We want to show we can make a synthetic equivalent and measure the forces in the motor.’

So why not use Nature’s own motors? Feringa refers to a quote by physicist Richard Feynman: what I can’t create, I don’t understand. ‘I really want to know how these molecular machines work and, like Feynman, I believe the best way to do so is to try and build one yourself.’ Even if it takes years to do so. ‘That’s why I’m pleased with the funding we’ve just obtained. It’s meant for basic research, so we can use it to study how these motors work. The grant will allow me to hire three or four PhD students.’

A second project for which the TOP Grant will come in handy is the design of a new molecular car. In 2011, Feringa and his team made it to the cover of Nature with the world’s first molecular four-wheel drive. It was made from four molecular motors and fuelled by light, and it moved over a surface of copper atoms. ‘We could point it in a certain direction and make it move, but now we want more’, Feringa explains. ‘We’d like to make it follow a kind of road, just like transporters in real living cells.’

Furthermore, the four-wheel drive will become a two-wheel truck, with two motors attached to a frame that should eventually carry a load. ‘And what’s more, we want it to work under normal conditions, not in the high vacuum we used for our previous model.’

Such a transport vehicle requires a delicate balance between attachment to the ‘road’ and the ability to move. ‘If it’s attached too tightly, it won’t move. If it’s too loose, it’ll be blown away by the Brownian storm.’ The random Brownian motion of very small particles at the molecular level is a force to be reckoned with.

Natural transporters in the cell have perfected this balance. ‘They’ve had billions of years of evolution for this, of course’, says Feringa. Seen in that light, it’s nothing to be ashamed of if his group needs a couple of years to complete the project.

The motors and the car he wants to make will just be the starting point. ‘Like the first transistor ever built or the first plane built by the Wright brothers: they’re nothing like the transistors in our present- day electronics or modern aircraft.’

Once again, if Nature has already perfected such devices, why make them yourself? ‘Nature’s way to fly is a bird. But our aircraft work by totally different principles, and they work very well.’ Simply copying Nature doesn’t generate the best results. So what could these synthetic molecular motors do?

Of course, the future is hard to predict, but some applications could be close at hand. ‘We’re working on a pore protein complex that can be opened or closed using a light-driven molecular switch’, says Feringa. If these pores are placed in artificial vesicles, they could be used in drug delivery, for example.

‘We’re also working on attaching a synthetic motor to proteins or DNA.’ Activating the motor would change the configuration of the attached molecule and thereby alter its function. ‘Eventually, this technique could be used to regulate biological processes.’ A striking example of this can be seen in a recent publication by Canadian scientists: they used such a device to control neurotransmission in a zebrafish. ‘They could switch off the motor neurons and literally stop the fish moving. That’s really fascinating.’

Gravitation Grant

Ben Feringa belongs to a consortium of scientists who were awarded a EUR 26.9 million ‘Gravitation Grant’ last autumn for a Research Centre for Functional Molecular Systems. They come from the universities of Nijmegen, Eindhoven and Groningen, and Feringa is the coordinator and one of six team members from the University of Groningen. The other staff members involved are Gerard Roelfes, Suzy Harutyunyan, Wesley Browne, Sijbren Otto and Anna Hirsch.

‘The aim of our proposal is to study supramolecular chemistry, the chemistry of complex systems on the boundary between living and non-living matter’, Feringa explains. Part of the project is to study chemical evolution, which preceded Darwinian evolution. ‘We want to know how processes like self-assemblage and self-replication work. This may eventually lead to the design of totally novel materials with, for example, the ability for self-repair.’

But the basic scientific questions are driving the project. ‘And they’re extremely exciting. Let’s face it, the question of how life first arose on our planet, our own beginnings, that’s a really big question to get your teeth into.’

The new Research Centre builds on cooperation between the principle investigators that goes back more than twenty years. ‘We all have worldwide reputations in the field of supramolecular chemistry. We’re very proud we’ve been awarded this large grant, as the competition was fierce. Funding for basic research is increasingly scarce, and this will allow us to appoint around six to eight PhD students a year in Groningen alone.’

In all, six Gravitation Grants were awarded out of 48 proposals.