Protein threading paves the way for nanomachines

A team of Dutch and Italian researchers has discovered how proteins are threaded through pores in cell membranes. They say the research throws light on the mechanisms by which viruses infect cells and will speed the creation of molecular machines.

Researchers led by Alan Rowan at the Radboud University Nijmegen in the Netherlands mimicked natural systems by threading synthetic polymer chains through ring-shaped molecules called macrocycles - molecules akin to nano-sized membrane pores.

By studying the kinetics of the threading process, they showed that for longer polymers the most favourable route requires an initial recognition step. ’We found that there has to be some sort of weak interaction between the ring and the polymer,’ says Rowan. ’So one part of the polymer is stuck to the outside of the hole and then there’s a loop where the end of the chain comes back into the hole.’

Thanks to favourable supramolecular interactions between the polymer and the pore, the threading process is energetically ’downhill’, so it is automatically driven in the right direction. At a fundamental level this explains how, in nature, membrane pores and macrocycles effectively suck in polymers and spit them out the other side, explains Rowan. ’The reason this is interesting is because a ring moving over a polymer is the exact same as through a hole, so the whole concept of transfection - viruses infecting cells - is that they’re pushing proteins through holes. The mechanisms in principle are exactly the same,’ he says.

The researchers say their work also creates a starting point for molecular-scale motors and machines based on such looping mechanisms. It is still early days, cautions Amar Flood, a molecular machines expert at Indiana University, Bloomington. But he thinks Rowan’s work will allow researchers to start building unidirectional motion into their molecules, dispensing with the need for an external driving force. ’They’ve done a great job of understanding the fundamentals and you have to do that if you want to make headway in mimicking what biology does - and in going beyond what biology does,’ he says.

Hayley Birch

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