Gibson Group News
New Paper in European Polymer Journal
Our latest work investigating how the architecture (shape) of synthetic ice growth inhibitors affects their function is now online in the European Polymer Journal. We have previously shown that poly(vinyl alcohol) is a potent inhibitor of ice crystal growth; a proeprty normally only found in antifreeze (glyco) proteins from polar fish species. We have also found that inhibiting ice growth lets us enhance the cryopreservation of donor cells, for regenerative medicine. However, we are still not certain of how this polymer functions. In this work, we developed a new tri-functional RAFT (or MADIX) agent to enable us to make 3-arm, star branched polymers. We foudn that the third arm was essentiall non-active, having the same activity as a 2-arm star (i.e. linear polymer). This suggests that hydrodynamic volume, not valancy (number of potental binding sites) is the key marker of activity and might suggest that the mode of action is not entirely due to direct ice binding
Read the paper here
Synthesis of Star-Branched Poly(vinyl alcohol) and Ice Recrystallization Inhibition Activity
Paper Published in Biomacromolecules
Our latest work has been published in ACS Biomacromolecules. This paper describes our latest progress in the design, understanding and application of synthetic polymers to mimic the function of antifreeze proteins. We have previously identified that poly(vinyl alcohol), PVA, is an excellent inhibitor of ice growth and can aid in the cryopreservation of cells. However, we do not really understand why it works so well, compared to other similar polymers. To address this, we made use of block copolymerization with a non-antifreeze active hydrophilic second polymer. This is a major advantage of using polymers, not proteins, in that macromolecular architecture can be easily changed. Here we find that addition of very large second blocks have essentially no effect of the antifreeze proteins of the PVA - even with block co-polymers where 90% is non-active polymer the activity is retained. This is a surprise and we believe (but cannot prove yet) that this indicates our PVAs do not bind the ice, but rather limit transfer of water at the quasi-liquid interface.
Read the paper here!
Paper Published in Journal of Materials Chemistry B
Our latest work has been published in the RSC Journal of Materials Chemistry B. This work forms part of our long standing interest in responsive nanomaterials - materials which can respond to biochemical (or external) triggers to promote a useful interaction. In particular we are interested in gold nanoparticles with responsive coronas. We have previously observed that the size of the particle core has a huge impact on the observed transition temperature of the hybrid particle. In this paper we investigated in detail the effect of mixing different sizes of particles, or identical particles with different polymers on them as a route to fine-tune the transition temperature; this is improtant as it removes the need to screen lots of polymers to obtain the desired response, as two 'master' batches can simply be mixed. In particular we found evidence for interaction betwen large/small particels with different transition temperatures, suggesting they have some cooperative aggregation behaviour. This, in particular, has applications and implications in the design of nanoparticle biosensors
Read the paper here
Paper published in Nanotoxicology
Our latest work, as part of a long term collaboration with JGU Mainz, has been published in the leading toxicology journal Nanotoxicology. Despite the huge interest in nanomedicine and drug delivery, succesful (clinically relevant) strategies to deliver across complex barriers, especially the blood brain barrier (BBB) are still missing. Here, we used a combinatorial synthethetic strategy (see here) to make a small library of polymer-coated gold nanoparticles as model nanoparticles to probe their interaction with the human BBB. Rather than just simply testing for cytoxicity (i.e. concentration to cause cell death) a detailed study was undertaken at low concentrations to look for other markers of toxicity. It was found that certain nanoparticle formulations lead to upregulation of pro-inflammatory markers. It was also possible to rule out ER (endoplasmic reticulum) stress, which can lead to apoptosis (programmed cell death). The versatile synthetic methodology, and unique properties of gold (SPR band) and ability to quantify cell uptake usign ICP was crucial to this. Read the full paper here.
Paper Published in Biomacromolecules
Our latest work has been published in the ACS journal Biomacromolecules. In this, we describe the synthesis and characterisation of surface-grafted polymer chains. We are very interested in making materials which can bind to biological targets, which means we need synthetic methods to incorporate appropriate ligands. One tool is micro-arrays, but these suffer from non-specific binding of proteins and cells, which can complicate the interpretation of the results. Hydrophilic polymers can help reduce this binding, and provide 'handles' for adding ligands. In this work, we used RAFT polymerization - which produces a thiol at every chain end to graft polymers directly on glass slides using a 'thiol-ene' reaction and compared this to using gold surfaces. We think these surfaces will be useful, esepcially in glycomics and glycobiology, as responsive microarray substracts, which we are now investigating
Read the paper here
Paper featured on front cover of Biomaterials Science
Our latest paper on cell cryopreservation has been selected by the editors of Biomaterials Science to feature on the front cover.
Read the paper here
Paper Published in The Analyst
Our latest work on exploiting carbohydrate interactions in diagnostics has been published in the RSC Journal The Analyst. We are very interested in expoiting carbohydrate (Glycan)-Protein interactions in the context of infectioud disease. For example, the symptons of Cholera poisoning (a global health issue) are caused by a carbohydrate binding protein (the Cholera Toxin). By creating nanostructures with the sugar on them, we hope to be able to detect disease at an early stage to inform clinicians and also enable appropriate use of a rapidly declining suite of antimicrobial agents. However, glycans are very promiscuous and not suited to sensors.
To overcome this we use multiplexing; essentially looking at multiple binding events, rather than 1, and generate a 'barcode' specific to the protein/pathogen. In this paper we extend this methodology to colour-changing gold nanoparticles to extract not only identification information but also concentration; a real challenge. The lead author on this paper was Dr Sarah-Jane Richards in the Group and also featured a masters research student (Denise)
Read the paper here; http://pubs.rsc.org/en/content/articlelanding/2016/an/c6an00549g#!divMetrics
Paper Published in Biomaterials Science
Our latest work on the use of polymeric ice recrystalisation inhibitors (IRIs) has been published in RSC Biomaterials Science. We have developed a series of polymers which mimic the function of antifreeze proteins, which are found in many species to enable them to survive freezing/sub zero temperatures. In this work we sought to build on our previous observations on enhancing red blood cell cryopreservation to 'harder' nucleated cell types (here and here). Typically these cells require the addition of organic solvents (DMSO) as cryoprotectants to enable them to be stored in the freezer but these can inhibit cell function, profileration and can be cytotoxic. Use several 'immortalized' (types widely used in research labs) cell lines we were able to enhance DMSO mediated cryopreservation by addition of the polymers. To really push this method, we also used primary (i.e freshly harvested) hepatocytes and found enhanced recovery.
The ability to bank cells is crucial for regnerative medicine to become a clinical reality and improved cell storage would be useful in reserach labs too. This work was a collaboration with Warwick Medical School (Dan Mitchell, Manu Vatish) and Einstein College of Medicine (Jeff Pesin).