Fantastic Plastic

A new type of monomer derived from amino acids and proteins borrows techniques from the pharmaceutical industry – and could lead to a host of new plastics in future, reports Lou Reade

A new polymerisation technique, which owes more to biology than it does to industrial chemistry, offers a promising way of making a new breed of plastic materials. US researchers say their method, which uses amino acids, rather than petrochemical fragments, as building blocks, could one day be used to ‘design’ a wide array of polymers with properties such as high stiffness or self-lubrication.

The researchers, from the Universities of Pennsylvania and Delaware, say that these ‘bundled monomers’, or ‘bundlemers’ as they have named the new type of monomer unit, are designed using computational chemistry (Nature, doi: 10.1038/s41586-019-1683-4). This helps to narrow down the most promising candidates – for features such as specific physical attributes, which are then synthesised and tested.

‘Computational chemistry is absolutely vital to this work,’ says Christopher Kloxin, assistant professor of materials science and engineering at the University of Delaware, and one of the lead researchers in the team.

The bundlemer unit is much larger than a typical plastic monomer and consists of multiple amino acids joined together to form a rod-like molecule. It might contain around 120 amino acids. After polymerisation, the high rigidity of the resulting polymer chain, compared with a typical plastic, could lead to novel polymers with high stiffness and strength.

Bundlemer-based polymers currently only exist in aqueous solution; however, they have been tested, and found to have a number of interesting properties. One of the most notable is being they form fibre-like structures around 30µm long – but only a few nanometres in diameter. Hence, bundlemers have more stiffness per monomer weight than any known synthetic or natural polymer, say the researchers.

‘There’s a basic premise in materials: if you can control function and structure, you can build anything,’ says Kloxin. ‘We have a well-defined structural unit, to which we can add chemical functionality at any location.’

Standard polymers

Conventional polymers are typically made from simple monomer units joined end to end to form various plastics. The simplest monomer unit is ethylene also known as ethene. Polymerisation using catalysis and high temperature and pressure makes use of the double bond of ethene, which breaks and adds to another molecule of ethene, forming a C-C single bond. The process is repeated many times to form the polymer.

This process is similar for other industrial polymers, where monomers such as propylene and vinyl chloride are used to make polymers such as polypropylene and PVC, for instance. While some polymers can now be derived from sustainable sources like sugar or maize – rather than petrochemicals – they all have a similar carbon ‘backbone’.

Bundlemers are a different type of monomer. For a start, they use amino acids as their basic building block. In addition, the molecules are highly designed, in a way more akin to pharmaceutical manufacture than polymer manufacture.

The bundlemer unit

Amino acids are the building blocks of biological molecules such as peptides and proteins. They are characterised by having an amine group and a carboxyl group. In living systems, amino acids join together into long strings called peptides – and the amine-carboxyl bond is known as a peptide bond. Peptides form the basis for complex biological molecules such as proteins.

There are 21 amino acids common to all life forms, but this is just a tiny proportion of all possible structures. The team takes advantage of this, by incorporating ‘non-natural’ structures into its bundlemers.

The researchers believe that bundlemer polymers could find their way into many different types of application – from commodity plastics to specialised materials. The potential to design strong, highly rigid materials could make them useful in engineering applications, such as construction.

‘High stiffness polymers and silk substitute are good examples – as are liquid crystals, membranes and drug delivery systems,’ says Kloxin. ‘These are all mentioned in a filed patent application.’

Limiting choice

The most basic challenge is to come up with practical bundlemer designs from such a broad spectrum of raw materials. Using just 20 of the ‘natural’ amino acids, there are more than 10 trillion ways of making a 10-molecule chain, say the researchers. Add to this the ability to use ‘non-natural’ amino acids – and ‘decorate’ them with side chains – and the permutations are almost infinite. The question is: where do you start?

‘We start with Jeffery Saven – who comes up with a building block “palette”,’ says Darrin Pochan, Chair of the department of materials science and engineering at the University of Delaware. ‘The structure is all decided in the computer.’

Saven, professor of chemistry at the University of Pennsylvania, uses models to design and analyse amino acid sequences with promising properties, which may be worth synthesising and testing. The bundlemer’s structure is a so-called ‘coiled coil’ peptide unit – a structure seen in some proteins. When produced, the bundlemers adopt a helical structure.

There are two parts to the molecule: the ‘core’; and the outside. The core – effectively the ‘spine’ of the molecule – does not change. Amino acids on the outer part will have a greater role in determining physical properties, and these are the ones that will be amended.

‘Natural systems make use of a variety of monomers – an “alphabet” – to create biopolymers with exquisite structures, functions and materials properties,’ says Saven.

These ‘information-rich’ systems use multiple types of monomers and show precise control of the chemical linking between the monomers. In a similar way, bundlemer systems will lead to the creation of new classes of polymers, he says.

Once the models are complete, Saven, Kloxin and Pochan discuss the pros and cons of each structure – and decide what physical characteristics they want for the polymer.

‘Some sequences might be easier to make than others, or you might run into an issue with solubility, which can be hard to anticipate from computation,’ says Saven.

In the Nature paper, the team linked 29 amino acids to make a peptide, then joined four peptides together to make a single bundlemer unit. Each bundlemer was made using solid phase peptide synthesis – again, a common technique used in the biological sciences.
Two different bundlemers were made: one terminated in maleimide groups, a non-natural termination for an amino acid; the second ended with the amino acid cysteine, which includes a thiol group. Solutions of the two bundlemers were mixed and left to react. The ease of reaction between the maleimide and thiol groups helped to ensure the production of long polymer chains from the two bundlemers.

Afterwards, the polymer-containing solution was slowly concentrated by air drying, and the resultant crystals were analysed and characterised using transmission electron microscopy. This revealed ‘extreme chain stiffness’, noted the researchers. The size and structure of the bundlemers was confirmed through neutron-scattering experiments.

Using peptide synthesis to string amino acids together is an established technique in the pharmaceutical industry, for example, but is highly specialised – and too expensive – for general use in materials science. Pochan says he is often challenged on the cost of making bundlemers using this method. A potential way of overcoming this in future would be to use recombinant technology – in which bacteria are engineered to produce the amino acid sequence in large quantities.

‘Industry does this all the time,’ he says. ‘There’s no reason ours could not be made the same way, which would make it more of a commodity.’

A bit on the side

One refinement, which is very difficult to achieve with conventional polymers, is to branch out the molecular structure from the one-dimensional ‘rod’ into a two dimensional ‘sheet’. This has been achieved by building on the side groups that sit around the outside of the bundlemer structure, and this could form the basis of new types of nanostructured materials.

‘Beyond that, we could then build beyond sheet, and into the third dimension – but that’s in the future,’ says Pochan.

The ‘handles’ on the side of the bundlemer can also be used to attach a variety of side chains. In the paper, the researchers demonstrated how gold nanoparticles – functionalised with maleimide groups – could be attached in this way. However, there is a more interesting possibility, which the team is already working on, that might find practical use. Adding an ‘initiator’ to a side chain would allow conventional polymerisation to take place. This could be done using typical free-radical polymerisation, to create a so-called ‘bottle brush’ architecture.

‘People are interested in bottle brush architectures because they have interesting lubrication properties,’ said Kloxin. An example is lubricin – a natural protein that lubricates joints in the human body. Bottle brush polymers have been designed that mimic the function of lubricin. Kloxin says that the ability to control the structure of bundlemer polymers means that ‘bottle brush’ polymers could be designed with a high degree of precision.

While the detailed chemistry is critical to the creation of the bundlemers, it is ultimately the physical characteristics – the thin, rod-like structure – that defines the material’s behaviour. In this way, creating longer or shorter bundlemers will change the physical behaviour of the final polymer – as will the creation of 2D nanostructured ‘sheets’, or even 3D structures.

Material acceptance

Despite the promise of the technique, Kloxin says there is a degree of resistance from materials scientists due to the nature of the building blocks, which he admits, as a polymer scientist, he initially shared.

‘Peptides and proteins are “biological” stuff,’ he says. ‘We want people in the materials world to see that this is an excellent design unit. If we can get past that bias, I hope they’ll see the potential.’

Pochan adds that overcoming this attitude is a key challenge. ‘Combining biology and materials in a seamless fashion is an underlying goal,’ he says. ‘I want materials people to just see these as materials. I want bio people to say, “This is a cool use of biomaterials.” It’s our job to bridge that gap.’

The key to a new polymer being accepted in industry is its usefulness as a material. Pochan says that bundlemer-based polymers have the potential to meet one of the key trends in plastics right now: sustainability.

Firstly, he says, these amino acid-based polymers are derived from natural resources rather than petrochemicals. And secondly, one of the many functions that could be ‘engineered’ into bundlemer structures is degradation.

‘You could design the chemistry so that the material degrades back into amino acids at a measured rate,’ he said. ‘This means it’s potentially a very “green” platform.’

Combining biology and materials in a seamless fashion is an underlying goal. I want materials people to just see these as materials. I want bio people to say “This is a cool use of biomaterials.”
Darrin Pochan chair of the department of materials science and engineering, University of Delaware

Future plans

It’s a long journey to take a polymer out of aqueous solution and turn it into one that could be injection moulded and extruded like any bulk plastic. But the team believes it could be achieved in five or six years.

‘We want to make building blocks that exist in organic solvents – eventually – and later as bulk polymer,’ says Pochan. Right now, he says the most important hurdle is recruiting enough people to carry out the research, in the face of a continuing Coronavirus lockdown.

‘We can make fibres in the lab. There’s no reason the material could not eventually be processed in traditional ways,’ he says.

For now, a key challenge will be to establish methods and rules for designing bundlemers with controlled stability and presentation of targeted chemical properties – including reactive functional groups.

‘A subsequent challenge will be to understand how the structural, functional and materials properties of bundlemer polymers are encoded in the peptides – as well as their chemical and physical processing,’ says Saven.

The ability to design materials with high precision means that bundlemers could be used for a range of applications. ‘One of the ultimate goals is to have these available as a bag of resin,’ says Pochan. ‘It could also work at the opposite end – as very high end, specialised materials, for use in areas such as biomedical tools.’

The team believes that the rigidity of bundlemers could make them useful in a diversity of applications – from parachute silk to bulletproof vests. The key, says Pochan, is that every application would rely on a new – and highly designed – monomer.

‘If you want to make a polymer with new properties, you need a new monomer,’ says Pochan.

Charlotte Vacogne, senior project leader in polymer chemistry at UK-based TWI has carried out research in a similar area, although was not involved in the bundlemers project.

‘The computational design part of this work is particularly neat as it enables the chemist to know what amino-acid sequences will – through inter-molecular physical bonds – self-assemble into tetrameric bundles – bundlemers,’ she says.

Vacogne adds that the stiffness of the polymer rods, with a persistence length of over 30µm, is ‘outstanding in the polymer world’, and well supported by convincing TEM images and ‘cleverly crafted’ control experiments.

‘A limitation may lie in the costly, milligram-scale synthesis used to produce the peptides,’ she says. ‘However, this clickable alternating Lego concept is brilliant. We can only hope for the day gene sequencers and biologists are able to make bacteria produce cheap bundlemers.’