Pathogens invade their hosts by several mechanisms including binding to glycans (sugars) on our cell surface. This binding is a crucial stage in their infection cycle and understanding these processes and developing new diagnostics and treatments. In this work we used glycoyslated nanoparticles to investigate how carbohydrate-binding proteins on the surface of influenza (hemagglutinins) bind sialic acids. We used our gold nanoparticle platform to enable easy incorporation of the sialic acids at the ends of polymers immobilised onto the gold particles, ensuring they were colloidally stable but still capable of present the sialic acids. Using a range of assays we optimized their structure to maximise outputs. We then interrogated a panel of hemaglutinins from different influenza strains, including zoonotic (species-crossing) strains. Crucially, when influenza 'jumps species' (e.g. avian to human), the nature of the glycan it binds also changes, which we were able to rapidly map. These results showed that our nanoparticle platform is a suitable tool for interrogating viral surface proteins and for helping to understand zoonosis.

Read the paper here; Polymer-Stabilized Sialylated Nanoparticles: Synthesis, Optimization, and Differential Binding to Influenza Hemagglutinins

X-ray diffraction to probe the kinetics of ice-recrystallisation inhibition

We have a large program to discover and understand macromolecular cryoprotectants and new materials to control ice growth. This is typically assessed by end-point assays using averaged data from a small number of ice crystals. Here we make use of the University of Warwick's excellent X-ray scattering platform to show how we can use a 2-D detector on WAXS (wide-angle x-ray scattering) to monitor ice recrsytallisaton in a bulk sample enabling 100's of crystals to be sampled. This method enables easy access to kinetic information which is challenging to obtain from cryo-microscopy alone.

Matt has been awarded a 5 years, €2 Million European Research Council (ERC) grant to start in 2020 called 'ICE PACK'. The aim of this is to develop materials for storing biologics in the cold chain, with the aim of making advanced therapies more available through better transport. This will follow from his previous ERC grants (Starting and Proof of concept) which studied polymers which could prevent ice growth. News story is here.

Enhancement of Macromolecular Ice Recrystallisation Inhibition Activity by Exploiting Depletion Forces

We have shown that the ice recrystallisation inhibition of poly(vinyl alcohol) can be improved by the addition of other, inactive macromolecules, in this case poly(ethylene glycol). The additive causes a depletant effect in the liquid channels between ice grains, driving PVA out of solution and on to the the ice crystal surface.

These results give greater insight into the mechanism behind poly(vinyl alcohol)'s antifreeze activity and open up a new suite of tools we can use to make potent antifreeze/cryopreservation agents.

Polyampholytes as Emerging Macromolecular Cryoprotectants

This perspective is the first review type article on polyampholytes as cryoprotectants and it covers important contributions from both our group and other global leaders in this area.In this perspective we summarise typical methods of cryopreservation for mammalian cells and highlight some of the specific challenges. We then discuss the synthesis and properties of polyampholytes as macromolecular cryoprotectants and detail ways in which polyampholytes have been used to enhance mammalian cell cryopreservation. We further hypothesise about their specific function and how this exciting new field will develop.

- A new polymer that's a cryoprotectant dramatically improves the freezing of cells, has been discovered by Gibson Group researchers at the University of Warwick

- The new polymers can reduce the amount of organic solvent required in cryopreservation (freezing cells) as well as giving more and healthier cells after thawing.

- Findings may help reduce cost and improve distribution of cells for cell-based therapies, diagnostics and research.

Cell freezing (cryopreservation) – which is essential in cell transfusions as well as basic biomedical research – can be dramatically improved using a new polymeric cryoprotectant, discovered at the University of Warwick, which reduces the amount of ‘anti-freeze’ needed to protect cells.

The ability to freeze and store cells for cell-based therapies and research has taken a step forward in the paper ‘A synthetically scalable poly(ampholyte) which dramatically Enhances Cellular Cryopreservation.’ published by the University of Warwick’s Department of Chemistry and Medical School in the journal Biomacromolecules. The new polymer material protects the cells during freezing, leading to more cells being recovered and less solvent-based antifreeze being required.

Cryopreservation of cells is an essential process, enabling banking and distribution of cells, which would otherwise degrade. The current methods rely on adding traditional ‘antifreezes’ to the cells to protect them from the cold stress, but not all the cells are recovered and it is desirable to lower the amount of solvent added.

The new Warwick material was shown to allow cryopreservation using less solvent. In particular, the material was very potent at protecting cell monolayers – cells which are attached to a surface, which is the format of how they are grown and used in most biomedical research.

Having more, and better quality cells, is crucial not just for their use in medicine, but to improve the quality and accessibility of cells for the discovery of new drugs for example.

Cell-based therapies are emerging as the “fourth pillar” of chemo-therapy. New methods to help distribute and bank these cells will help make them more accessible and speed up their roll-out, and this new material may aid this process.

Our latest work in the design of new materials to mimic complex glycan function and to inhibit bacterial toxins has been published in ACS Macro Letters. We have previously shown that synthetic polymers bearing carbohydrates in specific orientations or densities on polymer chains can give rise to increased affinity towards bacterial lectins (toxins) and may have application as decoys to prevent infection. However, many glycopolymers are rather basic simply having lots of glycans on a flexible polymer chain. In this work, we collaborated with Prof Filip du Prez (Gent, Belgium) using their thiolactone chemistry to enable us to introduce two functional units per repeat unit of the polymer. This was advantageous as it enabled us to mimic how GM-1 - a glycolipid on our cells - presents its glycans, but in a very simple manner. Using this, we made a library of glycopolymers with either 2 glycans or a hydrophobic unit. Using a combination of inhibitory assays and biolayer interferometry we unraveled the crucial design features to obtain highly active inhibits of lectin binding. This approach shows that moving from 'boring' homo-glycopolymers to those of increased complexity may help guide the development of materials to address the spread of infection.

Read the paper here

Double-Modified Glycopolymers from Thiolactones to Modulate Lectin Selectivity and Affinity

Our latest work into the design of new materials to inhibit toxins has been published in JPOLA. We urgently need new strategies to combat bacterial (as well as viral and fungal) infections due to the rise of antimicrobial resistance and the rapid evolution of some pathogens. Many pathogens, such as cholera or E.Coli secrete toxic proteins which bind to carbohydrates on our cell surfaces leading, which is their first step in infection. We have a major research program into the design and synthesis of new materials which can act as decoys for these toxins, preventing the infection from occurring. In this work, we evaluated a new range of polymers which instead of just having a single monosaccharide displayed multiple different ones. Our new synthetic strategy enabled this, and the rapid testing of the polymers ability to inhibit toxins. We showed that polymers bearing two difference sugars often were more potent inhibitors than those with just a single sugar, and this seemed to be linked the total capacity of binding (i.e. how many toxins the polymer can capture) rather than the actual affinity.

Read the paper here

Comparison of Systematically-Functionalized Heterogeneous and Homogenous Glycopolymers as Toxin Inhibitors.