January’s ‘Paper(s) of the Month’ come from the Gibson Group at the University of Warwick, a research group led by Dr Matt Gibson.
Matt and his group work at the interface of the organic and polymer chemistries with the life sciences, making use of modern polymer and organic methods to synthesise nano materials for various applications, including regenerative medicine, infectious disease and biotechnology.
Inspired by the evolutionary survival methods of polar region species, such as freeze avoidance using antifreeze (glyco)proteins (AFPs), the team has been working on the design and synthesis of polymer-based AFP mimics as novel new cryoprotectants for cell cryopreservation. They hope this will ultimately improve the availability of transplantable materials for regenerative medicine.
AFPs work by lowering the freezing point of water, and by preventing or slowing the growth of ice crystals. It is this ice recrystallisation inhibition (IRI) activity that is of particular interest to the Gibson group, as ice crystal growth during thawing is a major contributor to the failure of cryopreservation procedures.
Past attempts at using native AFPs for cryopreservation have shown they are not ideally suited to this application, but that a synthetic route to cryoprotectant molecules could be effective.
The group have successfully produced PVA polymers that mimic the function of AFPs, and have been using the Linkam BCS196 cryobiology stage to test their antifreeze properties. Their method employs gold nanoparticles as colourimetric probes for IRI, to allow high-throughput studies — it is hoped this will accelerate further investigations and discoveries of viable AFP mimics.
More recently they have also identified plant c-type lectins that display calcium dependent IRI activity, which indicates another possible approach to the development of synthetic AFP mimics.
The best technologies currently available for successful cryopreservation of cells and tissues involve adding large amounts of organic solvent, which has implications for future transplantation due to subsequent cellular toxicity. At present, blood for transfusions can only be stored for 42 days, and failure rates for transplantations increase rapidly with time since removal.
Improvements in the storage of cells (or tissues and organs in the future), through the use of cryopreservative AFP biomimics, would vastly improve the scope for regenerative medicine procedures and address an important unmet medical need.
By Frances Coles
Mitchell, DE., Congdon, T., Rodger, A. and Gibson, MI. (2015). Gold Nanoparticle Aggregation as a Probe of Antifreeze (Glyco) Protein-Inspired Ice Recrystallization Inhibition and Identification of New IRI Active Macromolecules. Scientific Reports 5, 15716.
Mitchell, DE. & Gibson, MI. (2015). Latent Ice Recrystallisation Inhibition Activity in Nonantifreeze Proteins: Ca2+-Activated Plant Lectins and Cation-Activated Antimicrobial Peptides. Biomacromolecules 16(10), pp 3411-3416.
Mitchell, DE., Cameron, NR. And Gison, MI. (2015). Rational, yet simple, design and synthesis of an antifreeze-protein inspired polymer for cellular cryopreservation. Chemical Communications 51, pp 19977-12980.