Being able to produce artificial spider silk has long been a dream of many scientists, but all attempts have until now involved harsh chemicals and have resulted in fibers of limited use. Now, a team of researchers from the Swedish University of Agricultural Sciences and Karolinska Institutet has, step by step, developed a method that works.
Today they report that they can produce kilometer long threads that for the first time resemble real spider silk.Spider silk is an attractive material–it is well tolerated when implanted in tissues, it is light-weight but stronger than steel, and it is also biodegradable. However, spiders are difficult to keep in captivity and they spin small amounts of silk. Therefore, any large scale production must involve the use of artificial silk proteins and spinning processes. A biomimetic spinning process (that mimics nature) is probably the best way to manufacture fibers that resemble real spider silk. Until now, this has not been possible because of difficulties to obtain water soluble spider silk proteins from bacteria and other production systems, and therefore strong solvents has been used in previously described spinning processes.
Spider silk is made of proteins that are stored as an aqueous solution in the silk glands, before being spun into a fiber. Researcher Anna Rising and her colleagues Jan Johansson and Marlene Andersson at the Swedish University of Agricultural Sciences and at Karolinska Institutet have previously shown that there is an impressive pH gradient in the spider silk gland, and that this well-regulated pH gradient affects specific parts of the spider silk proteins and ensures that the fiber forms rapidly in a defined place of the silk production apparatus.
This knowledge has now been used to design an artificial spider silk protein that can be produced in large quantities in bacteria, which makes the production scalable and interesting from an industrial perspective.
“To our surprise, this artificial protein is as water soluble as the natural spider silk proteins, which means that it is possible to keep the proteins soluble at extreme concentrations”, says Anna Rising.
To mimic the spider silk gland, the research team constructed a simple but very efficient and biomimetic spinning apparatus in which they can spin kilometer-long fibers only by lowering the pH.
“This is the first successful example of biomimetic spider silk spinning. We have designed a process that recapitulates many of the complex molecular mechanisms of native silk spinning. In the future this may allow industrial production of artificial spider silk for biomaterial applications or for the manufacture of advanced textiles”, says Anna Rising.
Learn more: Spinning spider silk is now possible
A chance meeting between a spider expert and a chemist has led to the development of antibiotic synthetic spider silk.
After five years’ work an interdisciplinary team of scientists at The University of Nottingham has developed a technique to produce chemically functionalised spider silk that can be tailored to applications used in drug delivery, regenerative medicine and wound healing.
The Nottingham research team has shown for the first time how ‘click-chemistry’ can be used to attach molecules, such as antibiotics or fluorescent dyes, to artificially produced spider silk synthesised by E.coli bacteria. The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) has been published in the online journal Advanced Materials.
The chosen molecules can be ‘clicked’ into place in soluble silk protein before it has been turned into fibres, or after the fibres have been formed. This means that the process can be easily controlled and more than one type of molecule can be used to ‘decorate’ individual silk strands.
In a laboratory in the Centre of Biomolecular Sciences, Professor Neil Thomas from the School of Chemistry in collaboration with Dr Sara Goodacre from the School of Life Sciences, has led a team of BBSRC DTP-funded PhD students starting with David Harvey who was then joined by Victor Tudorica, Leah Ashley and Tom Coekin. They have developed and diversified this new approach to functionalising ‘recombinant’ — artificial — spider silk with a wide range of small molecules.
They have shown that when these ‘silk’ fibres are ‘decorated’ with the antibiotic levofloxacin it is slowly released from the silk, retaining its anti-bacterial activity for at least five days.
Neil Thomas, a Professor of Medicinal and Biological Chemistry, said: “Our technique allows the rapid generation of biocompatible, mono or multi-functionalised silk structures for use in a wide range of applications. These will be particularly useful in the fields of tissue engineering and biomedicine.”
Remarkable qualities of spider silk
Spider silk is strong, biocompatible and biodegradable. It is a protein-based material that does not appear to cause a strong immune, allergic or inflammatory reaction. With the recent development of recombinant spider silk, the race has been on to find ways of harnessing its remarkable qualities.
The Nottingham research team has shown that their technique can be used to create a biodegradable mesh which can do two jobs at once. It can replace the extra cellular matrix that our own cells generate, to accelerate growth of the new tissue. It can also be used for the slow release of antibiotics.
Professor Thomas said: “There is the possibility of using the silk in advanced dressings for the treatment of slow-healing wounds such as diabetic ulcers. Using our technique infection could be prevented over weeks or months by the controlled release of antibiotics. At the same time tissue regeneration is accelerated by silk fibres functioning as a temporary scaffold before being biodegraded.”
The medicinal properties of spider silk recognised for centuries.
The medicinal properties of spider silk have been recognised for centuries but not clearly understood. The Greeks and Romans treated wounded soldiers with spider webs to stop bleeding. It is said that soldiers would use a combination of honey and vinegar to clean deep wounds and then cover the whole thing with balled-up spider webs.
There is even a mention in Shakespeare’s Midsummer Night’s Dream: “I shall desire you of more acquaintance, good master cobweb,” the character ‘Bottom’ said. “If I cut my finger, I shall make bold of you.”
‘I think we could make that!’
The idea came together at a discipline bridging university ‘sandpit’ meeting five years ago. Dr Goodacre says her chance meeting at that event with Professor Thomas proved to be one of the most productive afternoons of her career.
Dr Goodacre, who heads up the SpiderLab in the School of Life Sciences, said: “I got up at that meeting and showed the audience a picture of some spider silk. I said ‘I want to understand how this silk works, and then make some.’
“At the end of the session Neil came up to me and said ‘I think my group could make that.’ He also suggested that there might be more interesting ‘tweaks’ one could make so that the silk could be ‘decorated’ with different, useful, compounds either permanently or which could be released over time due to a change in the acidity of the environment.”
The approach required the production of the silk proteins in a bacterium where an amino acid not normally found in proteins was included. This amino acid contained an azide group which is widely used in ‘click’ reactions that only occur at that position in the protein. It was an approach that no-one had used before with spider silk — but the big question was — would it work?
Dr Goodacre said: “It was the start of a fascinating adventure that saw a postdoc undertake a very preliminary study to construct the synthetic silks. He was a former SpiderLab PhD student who had previously worked with our tarantulas. Thanks to his ground work we showed we could produce the silk proteins in bacteria. We were then joined by David Harvey, a new PhD student, who not only made the silk fibres, incorporating the unusual amino acid, but also decorated it and demonstrated its antibiotic activity. He has since extended those first ideas far beyond what we had thought might be possible.”
David Harvey’s work is described in this paper but Professor Thomas and Dr Goodacre say this is just the start. There are other joint SpiderLab/Thomas lab students working on uses for this technology in the hope of developing it further.
David Harvey, the lead author on this their first paper, has just been awarded his PhD and is now a postdoctoral researcher on a BBSRC follow-on grant so is still at the heart of the research. His current work is focused on driving the functionalised spider silk technology towards commercial application in wound healing and tissue regeneration.
Where will we be in 5 years’ time?
Dr Goodacre said: “It is likely that this paper is just the start of a very exciting range of studies using the new spider silk material. Some of the future work will also be supported by other, neat ideas from the world of spiders and their silk, which the SpiderLab is currently trying to unravel.”
Scientists at the UK’s Bangor and Oxford universities have achieved a world first: using spider-silk as a superlens to increase the microscope’s potential.
Extending the limit of classical microscope’s resolution has been the ‘El Dorado’ or ‘Holy Grail’ of microscopy for over a century. Physical laws of light make it impossible to view objects smaller than 200 nm – the smallest size of bacteria, using a normal microscope alone. However, superlenses which enable us to see beyond the current magnification have been the goal since the turn of the millennium.
Hot on the heels of a paper (Sci. Adv. 2 e1600901,2016) revealing that a team at Bangor University’s School of Electronic Engineering has used a nanobead-derived superlens to break the perceived resolution barrier, the same team has achieved another world first.
Now the team, led by Dr Zengbo Wang and in colloboration with Prof. Fritz Vollrath’s silk group at Oxford University’s Department of Zoology, has used a naturally occurring material – dragline silk of the golden web spider, as an additional superlens, applied to the surface of the material to be viewed, to provide an additional 2-3 times magnification.
This is the first time that a naturally occurring biological material has been used as a superlens.
In the paper in Nano Letters (DOI: 10.1021/acs.nanolett.6b02641, Aug 17 2016), the joint team reveals how they used a cylindrical piece of spider silk from the thumb sized Nephilaspider as a lens.
Dr Zengbo Wang said:
“We have proved that the resolution barrier of microscope can be broken using a superlens, but production of manufactured superlenses invovles some complex engineering processes which are not widely accessible to other reserchers. This is why we have been interested in looking for naturally occurring superlenses provided by ‘Mother Nature’, which may exist around us, so that everyone can access superlenses.”
Prof Fritz Vollrath adds:
“It is very exciting to find yet another cutting edge and totally novel use for a spider silk, which we have been studying for over two decades in my laboratory.”
These lenses could be used for seeing and viewing previously ‘invisible’ structures, including engineered nano-structures and biological micro-structures as well as, potentially, native germs and viruses.
The natural cylindrical structure at a micron- and submicron-scale make silks ideal candidates, in this case, the individual filaments had diameters of one tenth of a thin human hair.
The spider filament enabled the group to view details on a micro-chip and a blue- ray disk which would be invisible using the unmodified optical microscope.
In much the same was as when you look through a cylindrical glass or bottle, the clearest image only runs along the narrow strip directly opposite your line of vision, or resting on the surface being viewed, the single filament provides a one dimensional viewing image along its length.
“The cylindrical silk lens has advantages in the larger field-of-view when compared to a microsphere superlens. Importantly for potential commercial applications, a spider silk nanoscope would be robust and economical, which in turn could provide excellent manufacturing platforms for a wide range of applications.”
James Monks, a co-author on the paper comments: “it has been an exciting time to be able to develop this project as part of my honours degree in electronic engineering at Bangor University and I am now very much looking forward to joining Dr Wang’s team as a PhD student in nano-photonics.”