Dressing up biology like a circuit board…

by Jim Caryl

WHAT’S this then?

This is an electron-micrograph (a picture taken through an electron microscope), taken at 56,000x magnification. It also happens to have been taken by me. What you’re looking at is a filament of protein, called an ‘amyloid fibril’.

Nanowire filament

The straight fibril that runs from the centre of the picture to the the bottom-right, is 0.5 microns in length (about quarter of the length of an E. coli cell, or 1/2000 of a millimetre). Each of those dots is a sphere of gold that is 5 nanometres in width.

To understand something about amyloid, we need to do some very basic revision on what proteins are:

  • Some proteins make up the structure of your body’s tissues;
  • some act as cellular emails, enabling cells to talk to each other; and,
  • some are also known as enzymes, and perform almost all of the millions of biochemical reactions that result in you.

Proteins are made of chains of amino acids, and as these are Daisy-chained together in each of your cells they fold into very specific 3D shapes. Each shape is unique, determined by the sequence, and type, of amino acids making up the chain; this gives each protein their specific role.

However, things don’t always go according to plan, and for some reason proteins occasionally mis-fold. When this happens there are usually repair mechanisms to deal with the mis-folded protein, but some proteins naturally mis-fold and aggregate into an alternate stable structure; amyloid.

Amyloid is medically important for several reasons, not least of which is because it is insoluble, and starts to form meshes of material that can collect in various parts of the body. It is the build up of such amyloid ‘plaques’ in between brains cells (neurons) that is one of the hallmarks of Alzheimer’s. Alternatively, people on long-term dialysis, perhaps due to kidney failure associated with diabetes, also suffer from a build up of amyloid in the joints; so-called ‘dialysis-related amyloidiosis‘. This is a debilitating condition that slowly erodes the joints, causes numbness, swelling and numerous other clinical problems.

So what has this got to do with the above picture?

Bionanotechnologies research makes use of the knowledge that biologists have developed about the various systems they have characterised, and uses it for completely new and often unexpected functions. There is a great deal of bionanotechnological science going out there; it is being developed for medical purposes, often as a new means of targeting drugs directly to the cells that need them, or to specific harmful bacterial strains; and for advanced biosensors and diagnostic tools.

Another use is in nanoelectronics, or specifically nano-bioelectronics. The basis of such research is that, technologically, we are slowly approaching the limit of miniaturisation of electronic circuits, which is a problem if you’re trying to squeeze more transistors onto your next-generation cpu (the brain of your computer hard-drive). Previous technologies have worked from a ‘top-down’ approach, gradually making each component smaller and smaller. However, there comes a point when the components are so small, and so close together, that neighbouring components starts to have a negative effect on each other; this is playfully known as ‘electro-smog’.

An alternative route is to work from the ‘bottom-up’; start with the smallest molecules possible, and gradually build a circuit on a nano-scale, which in our lab generally encompasses molecules up to the size of 100 nm (nanometers), which is about 1/10,000th of a millimetre on a ruler. However, how does one go about making electronic circuits that are so small? One way is to use self-assembly, and if there’s one thing that biologists know about, it’s self-assembly. We know that one strand of DNA binds to its complementary strand of DNA, in the form of DNA base-pairs. We know that certain proteins bind to other proteins, or to certain sequences of DNA. By understanding these processes, we can design circuit boards that quite literally self assemble.

In the picture above, this was an attempt to make a single wire (a nanowire) out of a filament of protein, for just such a nano-circuit board. Of course, these filaments are no good for conducting electricity on their own; they are only the scaffold onto which we plaster a metal, such as gold, which does conduct electricity. So, firstly we’ve got to change the properties of the individual proteins that make up the amyloid filaments, so that gold now likes to bind to them; then we can add gold in the form of gold nanoparticles. In the picture above you can see the gold nanoparticles as small spheres, only 5 nanometres wide, each consisting of a cluster of around 100 gold atoms. We buy the gold in a solution, and as the nanoparticles are so small, they just float around, never settling, and appear red coloured to the eye.

Once the gold nanoparticles coat the the amyloid we need to join-the-dots, so to speak. The metal needs to be touching for electricity to pass, so we simply add more gold, but this time free-atomic gold, which fills in the spaces. We then bake the wires at a very high temperature, to melt all the gold into one long wire, and then test to see if it conducts electricity.

So this is just one of the many uses of our understanding of biology that can be applied to completely different areas of science and technology, and is an interesting by-product of the active research being undertaken to address important medical conditions.

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