Making molecules work

The operation of most living organisms, from bacteria like E. Coli to multi-cellular organisms like ourselves, depends on molecular motors. These are protein-based machines which convert chemical energy to mechanical energy; the work our muscles do depends on many billions of these nanoscale machines all operating together, while individual motors propel bacteria or move materials around inside our cells. Molecular motors work in a very different way to the motors we are familiar with on the macroscopic scale, as has been revealed by some stunning experiments combining structural biology with single molecule biophysics. A good place to start getting a feel for how they work is with these movies of biological motors from Ronald Vale at UCSF.

The motors we use at the macroscopic scale to convert chemical energy to mechanical energy are heat engines, like petrol engines and steam turbines. The fuel is first burnt to convert chemical energy to heat energy, and this heat energy is then converted to useful work. Heat engines rely on the fact that you can maintain part of the engine at a higher temperature than the general environment. For example, in a petrol engine you burn the fuel in a cylinder, and then you extract work by allowing the hot gases expand against a piston. If you made a nanoscale petrol engine, it wouldn’t work, because the heat would diffuse out of the cylinder walls, cooling the gas down before it had a chance to expand. This is because the time taken for a hot body to cool down to ambient temperature depends on the square of its size. At the nanoscale, you can’t maintain significant temperature gradients for any useful length of time, so nanoscale motors have to work at constant temperature. The way biological molecular motors do this is by exploiting molecular shape change – the power stroke is provided by a molecule changing shape in response to the binding and unbinding of the fuel molecules and their products.

In our research at Sheffield we’ve been trying to learn from nature to make crude synthetic molecular motors that operate in the same way, by using molecular shape changes. The molecule we use is a polymer with weak acidic or basic groups along the backbone. For a polyacid, for example, in acidic conditions the molecule is uncharged and hydrophobic; it takes up a collapsed, compact shape. But when the acid is neutralised, the molecule ionises and becomes much more hydrophilic, substantially expanding in size. So, in principle we could use the expansion of a single molecule to do work.

How can we clock the motor, so that rather than just expanding a single time, our molecule will repeatedly cycle between the expanded and the compact shape? In biology, this happens because the reaction of the fuel molecule is actually catalysed by the the motor molecule. Our chemistry isn’t good enough to do this yet, so we use a much cruder approach.

We use a class of chemical reactions in which the chemical conditions spontaneously oscillate, despite the fact that the reactants are added completely steadily. The most famous of these reactions is the Belousov-Zhabotinksy reaction (see here for an explanation and a video of the experiment). With the help of Steve Scott from the University of Leeds, we’ve developed an oscillating reaction in which the acidity spontaneously oscillates over a range that is sufficient to trigger a shape change in our polyacid molecules.

You can see a progress report on our efforts in a paper in Faraday Discussions 128; the abstract is here and you can download the full paper as a PDF here (this is available under the author rights policy of the Royal Society of Chemistry, who own the copyright). We’ve been able to demonstrate the molecular shape change in response to the oscillating chemical reaction at both macroscopic and single chain level in a self-assembled structure. What we’ve not yet been able to do is directly measure the force generated by a single molecule; in principle we should be able to do this with an atomic force microscope whose tip is connected to a single molecule, the other end of which is grafted to a firm surface, but this has proved rather difficult to do in practise. This is high on our list of priorities for the future, together with some ideas about how we can use this motor to do interesting things, like propel a nanoscale object or pump chemicals across a membrane.

This work is a joint effort of my group in the physics department and Tony Ryan’s group in chemistry. In physics, Mark Geoghegan, Andy Parnell, Jon Howse, Simon Martin and Lorena Ruiz-Perez have all been involved in various aspects of the project, while the chemistry has been driven by Colin Crook and Paul Topham.

5 thoughts on “Making molecules work”

  1. I am not so sure that heat cané─˘t be used to drive shape change in nano-scale machines. If you start with a polymer in water that is coiled into a tight conformation at one temperature and uncoils in water at a temperature a few degrees higher, all you need to do is find a way to selectively heat the polymer. I think you should be able to attach gold nano-particles to the polymer and use EM radiation to inductively heat the gold nano-particles. It would work like this,
    1.) you switch on your EM source
    2.) it heats the gold nano-particle
    3.) the gold nano-particle transfers the heat to the polymer
    4.) the polymer uncoils in the water
    5.) you switch off the EM source
    6.) the nano-scale machine rapidly cools back down
    7.) the polymer recoils back up.

    (I think that the recoiling of the polymer would be the power stroke.)

  2. Well, the thermal conductivity of water is about 1.5e-7 m2/s, so for a polymer molecule that’s 10 nm in its expanded size, we can estimate the characteristic time for the heat to diffuse away from this region to be about 1 nanosecond. The time it’s going to take the polymer to expand or contract is likely to be of order tens of milliseconds or longer. So while your scheme would work as long as you keep the energy source on long enough for the polymer to uncoil, most of the energy you put in is going to diffuse away and be wasted (a rough guess at the efficiency is simply given by the ratio of the two characteristic times, which here is going to be less that 1e-7). There will be some applications for which your scheme would be useful (for example in triggering the release of a drug from a carrier at some point in the body which you irradiate with laser light), but for any application where you need to have a respectable energy efficiency it’s not going to be competitive.

  3. pubs/hamad-schifferli-enn04.pdf

    The link above is to a paper (DNA Hybridization: Electronic Control) that explores the use of gold nano-particles to “melt” DNA structures. It looks like you can generate a temperature difference of at least 13 degrees C and you can heat up a sphere ~10 nm in diameter with an inductively heated gold nano-particle (1.4 nm in diameter).×0609.pdf

    This is another paper that explores using a DNA/gold nano-particle system to make electronically controlled nano-machines.

    But neither of the two papers described how inefficient the inductive heating system is at producing useful work, thanks for the heads up Richard.

    But, efficiency is not everything and having the ability to selectively heat up only several hundred cubic nanometers has got to be a pretty useful tool to have in the tool box. It not only allows you to control the physical melting/ freezing of some polymers but should also allow you to speed up chemical reactions occurring in that small volume.

  4. Thanks for a useful link, Jim. It’s clear that local heating is going to be very useful if you’ve got an external source of energy and you’re not bothered about efficiency, which is certainly going to be the case for lots of therapeutic applications. But it won’t work if you want to power an autonomous nanobot.

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