Bioadhesives Getting stuck in Nature produces a wide variety of glues that outperform all synthetic adhesives. Michael Gross looks into this sticky subject SCIENCE PHOTO LIBRARY PHOTO SCIENCE

52 | Chemistry World | December 2011 www.chemistryworld.org Glue is something we buy in plastic bottles or tubes, and apply to ‘clean, dry surfaces’. How then do mussels and barnacles stick to the hulls of ships and to the steel structures of piers exposed to seawater? If we leave a glue container open for a couple of hours, it dries out and becomes unusable. But carnivorous plants expose glue drops to the air waiting for an insect to stick to them, remaining sticky for as long as it takes. Clearly, nature knows a lot about gluing things together that we haven’t mastered yet. Thus, it would make sense to find out more about nature’s glues. But where to begin? There is a bewildering array of sticky materials in many different species of plants and animals, sharing few general principles other than being

sticky. Patrick Flammang from the FOTOSTOCK/SUPERSTOCK AGE University of Mons, Belgium, who chairs a European collaborative fine hairs, with a tiny droplet of Sea cucumbers expel weapon in their posterior body cavity project on natural adhesives – polysaccharide solution crowning sticky spaghetti-like consisting of sticky white threads, Biological adhesives: from biology the tip of each hair. When an insect tubules to trap attacking known as smooth cuverian tubules. to biomimetics – admits that the gets stuck on these, the leaf curls to organisms One end of each thread is attached field is difficult to survey. ‘The enclose it from all sides, allowing to the animal’s respiratory tree (its diversity of biological adhesives is for more efficient digestion. This lungs), while the other floats freely huge,’ he says, ‘but at the same time plant’s glue is a viscoelastic aqueous in the fluid that fills its body cavity, it represents an opportunity to look solution of a polysaccharide based the coelomic fluid. When the animal for adhesives with novel interesting on a repeating dimer of glucuronic feels threatened, it will point its properties.’ acid and mannose. Other sugars backside towards the disturbance including arabinose, xylose and and contract its entire body. The Caught in a trap galactose are found in its side chains contraction causes the spaghetti- Charles Darwin marvelled at the and end groups. There is nothing carrying cavity to burst open, and phenomena of carnivorous plants else present in the glue before an the fluid to erupt into the cloaca (the that snare insects for additional insect gets caught, only after capture posteria opening). The free ends of nutrition, publishing a book on does the plant leaf secrete digestive dozens of those spaghetti will be them in 1875. Many of these plants enzymes into the fluid. expelled via the cloaca and shot at use glue for this purpose, as it The glue from the Portuguese the hapless adversary. prevents the bugs escaping while sundew (Drosophyllum lusitanicum), The animal then pumps these the plant digests them. which Darwin obtained through tubules (still connected to the In his book, Darwin described a contacts in Portugal and described respiratory tree) full of water, which plausible evolutionary path from the in detail, has a similar composition extends them to a multiple of their use of sticky leaves for defence only, and is slightly acidic as it contains original length. When they hit a via the accidental uptake of nutrients ascorbic acid. It smells of honey surface (eg the suspected predator), from trapped insects degraded by and is strongly hygroscopic (it can the inflated tubes instantly develop bacteria, to the secretion of digestive collect water from fog). In a recent strong adhesive properties. In the enzymes enabling the plant to ‘eat’ review article, Wolfram Adlassnig last phase of the attack, the tubes the prey. Darwin also described the and colleagues from the University In short detach from the respiratory tree and first practical application of such of Vienna, Austria, concluded that  Natural adhesives the animal can take flight, leaving plants – people in Portugal used the glue of these species would currently outperform all behind a frustrated predator tangled them to keep houses free of insects. be an interesting material for synthetic glues up in a sticky mess. Given this illustrious history, pharmaceutical applications, as ‘it  The wide range of The black sea cucumber surprisingly little is known about the is non-toxic, remains stable under natural glues share few (Holothuria forskali) is the most molecular details and mechanisms varying environmental conditions, general principles other studied of these animals. The of action of the carnivorous plant and even exhibits antibiotic than being sticky material left on the trapped glues. They can be organised into properties’.1 However, other than  More fundamental predators once the tubules are two major groups: water soluble and its use for fly catching, no applied research is needed removed has been found to contain more fat soluble. research has been reported yet. before scientists can a mixture of 60 per cent protein Several carnivorous plant understand the secrets and 40 per cent carbohydrates. families, including Droseraceae and A sticky mess of their success Flammang’s group has studied Lentibulariaceae, produce water- Any marine predator that approaches  Natural and bioinspired the amino acid composition of the based polysaccharide glue. The a sea cucumber may end up looking glues are being considered protein portion and found that it house plant cape sundew (Drosera like they have had a nasty accident for medical applications is rich in glycine and other amino capensis), for example, has long with a bowl of spaghetti. Sea such as surgical adhesives acids with small side chains, and in leaves covered in hundreds of very cucumbers carry a bizarre defence and diabetes treatments charged and polar amino acids.2 www.chemistryworld.org Chemistry World | December 2011 | 53 Bioadhesives

‘Polar and charged amino acids are important for adhesive interactions with the surface. Different side chains (polar, positively charged and negatively charged) increase the number of possible interactions with the surface (Van-der-Waals, electrostatic etc),’ explains Flammang. ‘Small side chain amino acids are characteristic of the so-called elastomeric proteins, proteins that can deform considerably without breaking (eg elastin). This is important for the cohesive strength of the glue.’ While marine adhesive proteins from different groups of organisms can vary widely in their sequences, most of them share these fundamental aspects of their amino acid composition. Unlike the adhesive plaque proteins of mussels, the protein component does not appear to contain the modified amino acid 3,4-dihydroxyphenylalanine (Dopa). However, phosphorylation of another

amino acid – serine –previously ISTOCKPHOTO observed in mussel glue and tube worm cement, is present. forming strong adhesion, such that Barnacles and mussels Sticking together Currently, Flammang’s team is they are washed away by water are able to stick to Humans may have notions that analysing peptide fragments of the movement, have failed to stop diatom- structures immersed in love, mortgages, children and other glue proteins. The goal here is to based biofilms from growing.3 seawater shared interests keep couples identify the genes, allowing them to Nicole Poulsen and Nils Kröger together, but the northern spadefoot produce the pure proteins for more from the Georgia Institute of toad (Notaden melanoscaphus) of detailed analysis. The group has Technology in Atlanta, US, have just northern Australia – and three other also applied sugar-binding proteins launched a project to identify the species of the same genus – play it known as lectins to analyse the glue molecules of diatoms. ‘Diatom safe, using glue to make that special distribution of carbohydrates in the glues aren’t very well characterised bond. cuverian tubules. at the molecular level,’ Kröger says. These frogs (they are frogs, not There is more work to be ‘Lectin binding studies point to the toads as their name suggests) are so done, and the detailed molecular presence of carbohydrates, and well-rounded that they can’t cling on structure and adhesive mechanism the saw-tooth fingerprints you get to each other with their short limbs of the black sea cucumber glue still in force-distance plots when you during mating, like many other frog remains elusive. stretch the material in AFM [atomic species do. Instead they use glue to force microscopy] experiments stick together for the duration. Get it off me suggest the presence of protein Michael Tyler from the University While the sea cucumber is a glue domains.’ What exactly makes the of Adelaide, Australia, tested the producer we may want to emulate in diatoms stick and how one can stop Northern spadefoot toad adhesive power of the northern technology, interest in other marine them from doing so remains to be ‘couples’ glue themselves spadefoot toad secretions by using adhesives is directed towards the explored. together during mating it to stick two full, cold, wet beer question of how to stop them from cans together – lengthwise in one sticking to things. Organisms such experiment and bottom-to-top in as barnacles, mussels, bacteria and another. In both cases the frog glue algae find the steel structures that was strong enough to carry the humans immerse into their habitats weight of a full can. He also found – ship hulls and piers for example – that the glue can bind glass, plastics very appealing to settle on. and even ‘non-stick’ Teflon surfaces, This can cause significant no matter whether they are wet or problems. On ships, even simple dry, hot or cold. slime films consisting of bacteria Another team of Australian and diatoms (a group of algae) can scientists, led by Lloyd Graham increase fuel consumption by up at CSIRO Molecular and Health to 15 per cent. Antifouling coatings Technologies in Sydney, found that releasing heavy metals like copper the glue – which can be harvested or tin had some success, but were from living frogs by electrical banned due to their environmental stimulation – is protein-based. impact. Silicone-based coatings, It contains a range of proteins of

which should stop organisms from different sizes, which are rich in PICTURES/SUPERSTOCK MINDEN 54 | Chemistry World | December 2011 www.chemistryworld.org PHILLIP MESSERSMITH PHILLIP

glycine, proline, and glutamine or rates, so an insect flying into the web Byssal threads from and that this impedes efforts to glutamic acid.4 will get stuck in it. At low extension a mussel inspired mimic biological adhesives,’ says ‘Having demonstrated that the rates, when the prey is struggling the development of a Messersmith. ‘Each organism glue will adhere vertebrate tissues to get free, the material responds medical adhesive has its own features and and that it is non-toxic, the potential elastically, making it impossible for peculiarities, evolved under very for this glue to be used for surgical the insect to detach itself. strict environmental conditions repairs is virtually unlimited,’ Tyler – therefore it is difficult to make enthuses. ‘Orthopaedic and ENT Medical adhesives generalisations across species. [ear, nose and throat] surgeons The northern spadefoot toad Even “simple” biological adhesive are very keen to be able to use this secretion is not the only natural systems are exceedingly complex product following the success of glue being considered for surgical and may require years of research our animal studies. To proceed we applications. The hope is that to understand sufficiently to allow now need the collaboration of a biological – or bioinspired – for mimicry.’ major pharmaceutical company glues will be functional under A team effort to improve to underwrite the next stage of physiological conditions, non-toxic, fundamental knowledge, with the development.’ and ultimately biodegradable. ultimate aim of bringing innovative Other frog species (as with the Biomaterials scientist Phillip bioinspired adhesives to market, is sea cucumbers) use glue purely Messersmith from Northwestern exactly what Flammang is hoping for defence, as Alan Cooper from University at Evanston, Illinois, to achieve with his project. ‘Our the University of Glasgow, UK, US, has developed a glue inspired goal is fostering collaboration experienced during his research into by the chemical principles used by across disciplines, which is their foam nests (Chemistry World, marine mussels. The natural process important in order to develop July 2009, p40). ‘Several tropical involves proteins with the modified biomimetic adhesives for various frogs exude a sticky secretion amino acid Dopa, carrying a catechol applications,’ he says. from their skin as a defence group as a side chain. Introducing response when attacked – usually this group into the synthetic Michael Gross is a science writer to discourage snakes and other polymer polyethylene glycol, the based in Oxford, UK predators. I got caught out by this researchers can make a biomimetic ‘Even “simple” once in Malaysia when I grabbed a glue. Dixon Kaufman’s group at the biological References nice looking frog – it immediately same university has successfully 1 W Adlassnig et al, Biological adhesive systems: puffed itself up in my hand and tested this adhesive in an animal adhesives may from nature to technical applications, p15. exuded a sticky goo that took hours model for a new diabetes treatment, (J von Byern and I Grunwald Eds). Vienna, to wash off,’ Cooper reminisces. gluing islet cells to liver surfaces.5 require years Austria: Springer, 2010 2 P T Becker and P Flammang, Biological Other glue manufacturers in the To enable more biomedical of research to adhesive systems: from nature to technical animal kingdom include spiders applications to benefit from the applications, p87 (Chemistry World, December natural variety of glues, more understand 3 P J Molino and R Wetherbee, Biofouling, 2008, 2010, p42). Their glue, made up fundamental research is still needed. sufficiently 24, 365 (DOI: 10.1080/08927010902254583) of glycoprotein, behaves like a ‘It is certainly true that there is 4 L D Graham et al, J. Biomed. Mater. Res. A, to allow for 2010, 93, 429 (DOI: 10.1002/jbm.a.32559) viscoelastic solid. This means that the limited molecular understanding 5 C E Brubaker et al, Biomaterials, 2010, 31, 420 material is viscous at high extension of natural adhesive systems mimicry’ (DOI: 10.1016/j.biomaterials.2009.09.062) www.chemistryworld.org Chemistry World | December 2011 | 55