Our latest paper is ACS Editors' Choice Article
Optimization and Stability of Cell-Polymer Hybrids Obtained by ‘Clicking’ Synthetic Polymers to Metabolically-Labeled Cell Surface Glycans
Re-engineering of mammalian cell surfaces with polymers enables the introduction of functionality including imaging agents, drug cargoes or antibodies for cell-based therapies, without resorting to genetic techniques. Glycan metabolic labeling has been reported as a tool for engineering cell surface glycans with synthetic polymers through the installation of biorthogonal handles, such as azides. Quantitative assessment of this approach and the robustness of the engineered coatings has yet to be explored. Here, we graft poly(hydroxyethyl acrylamide) onto azido-labeled cell surface glycans using strain-promoted azide-alkyne ‘click’ cycloaddition and, using a combination of flow cytometry and confocal microscopy, evaluate the various parameters controlling the outcome of this ‘grafting to’ process. In all cases, homogenous cell coatings were formed with > 95% of the treated cells being covalently modified, superior to non-specific ‘grafting to’ approaches. Controllable grafting densities could be achieved through modulation of polymer chain length and/ or concentration, with longer polymers having lower densities. Cell surface bound polymers were retained for at least 72 hours, persisting through several mitotic divisions during this period. Furthermore, we postulate that glycan/membrane recycling is slowed by the steric bulk of the polymers, demonstrating robustness and stability even during normal biological processes. This cytocompatible, versatile and simple approach shows potential for re-engineering of cell surfaces with new functionality for future use in cell tracking or cell-based therapies.
Our latest work in ACS MacroLetters
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
New Glycopolymers for Toxin Inhibition is published
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
Paper Published in Macroletters
Our latest work has been published in ACS Macro Letters. In this work we describe a new method to covalent attached synthetic polymers to cell surfaces, enabling us to bring new functionality to them, without resorting to genetic methods. There already exist many chemistry for targetting cell surfaces, such as simple NHS esters, or lipid insertion, but we wanted to form a directed, covalent bond. Glycan metabolic labeling was exploited, whereby we added an azido-functional ManNac (a sugar) to the cells, which can be processed such that it presented an azide on the cell surface as sialic acid. We then made telechelic polymers used RAFT, adding an azide reactive strained alkyne at one end, and a fluorophore or biotin at the other. We would able to show selective conjugation and coating of the cells using these polymers, with no evidence of cytoxocity nor of morphological changes (i.e. the cells looked happy). To show that we can use this method to change the functionality of the cells, we were able to recruit streptavidin to the cell surfaces, targetting the biotin units on the polymer, which did not occur without the polymer. We think this method could be broadly used to add synthetic polymers to cell surfaces to modify their function, which may have application in therapies, cell tracking and also to ask fundamental questions about how this modification affects cell function.
Read the paper here
Paper Published in Langmuir
Our latest work has been published in Langmuir, as part of a special issue focussed on Mechano- and Cryo-biology, which we were very proud to be invited to contribute too. In this work, we ask the question of 'do our antifreeze-protein mimetic polymers function the same in nanoparticle form, as in solution'. This might seem straightforward, as we know that increasing the molecular weight of our polymers, increases their activity, hence when immobilised on a nanoparticle they might be more active. We actually saw that there was no enhancement, but also no decrease (which again is a surprise as the nanoparticles have a lower molar concentration than free polymers). We made use of RAFT/MADIX polymerization to make thiol-terminated poly(vinyl alcohol) to coat gold nanoparticles for this particular work, as model nanoparticle systems, which were tunable in terms of size and composition.
Read the paper here;
Professor Gibson speaks at Glycobiotechnology 2018
Professor Gibson spoke at the Glycobiotechnology 2018 event hosted at Manchester University. This was an event to celebrate and showcase UK Glycoscience research. Professor Gibson showed new research from the group in the design of dynamic glycomaterials, where we exploit polymer chemistry to control the presentation of specific glycans in response to external stimuli. He also highlighted the role of the RSC Carbohydrate Group, of which he is the present chair.
Professor Gibson Gives Keynote at EuCHems Conference
On 29th September, Professor Gibson gave the keynote lecture in the Biomaterials Stream of the 7th EuChems international Conference in Liverpool. In this, he discussed the groups latest research into using polymers to transform the Biologic Cold Chain. This included how to target ice crystals with polymers, and the cryopreservation of mammalian and bacterial cells as well as protein drugs.
Paper in ChemEurJ; Hot paper and Media Attention
Our latest work into developing non-traditional antimicrobial agents has been published in Chemistry: A European Journal. This continues our research into cationic polymers as antimicrobial agents. In this new work, we demonstrate a semi-automated synthesis platform, which can use robotics to speed up the liquid handling, alongside exploiting photo-chemical polymerization to enable this to take place in 'open air'; this is a key step as it removes the need for sealed vials and allowed us to polymerise directly in 96 well plates. 96 well plates are industry-standard for biological screening, which enabled us to rapidly screen ~ 100 polymers for antimicrobial activity, as well as blood compatibility. Using this high-throughput approach a surprising 'hit' was found, where including 15 mol % of oligopropyleneglycol methacrylate lead to a dramatic enhancement in bacteriostatic activity, but without introducing bacteriocidal activity.
Read the paper here
The paper was also featured in the media, and highlighted by the reviewers as being a 'hot' paper.