Microscopic versions of the cocoons spun by silkworms have been manufactured by a team of researchers.
The capsules, which are invisible to the naked eye, can protect sensitive molecular materials, and could prove a significant technology in areas including food science, biotechnology and medicine, say the researchers.
The capsules were made at the University of Cambridge using a microengineering process that combines the power of microfluidic manufacturing with the value of natural silk.
The process mimics on the microscale the way in which Bombyx mori silkworms spin the cocoons from which natural silk is harvested. The resulting micron-scale capsules comprise a solid and tough shell of silk nano-fibrils that surround and protect a centre of liquid cargo and are more than thousand times smaller than those created by silkworms.
The same technology could also be used in pharmaceuticals to treat a wide range of severe and debilitating illnesses. In the study, the researchers successfully showed that silk micrococoons can increase the stability and lifetime of an antibody that acts on a protein implicated in neurodegenerative diseases.
The work was carried out by an international team of academics from the Universities of Cambridge, Oxford and Sheffield in the UK; the Swiss Federal Institute of Technology in Zurich, Switzerland; and the Weizmann Institute of Science in Israel. The study was led by Professor Tuomas Knowles, a Fellow of St John’s College at the University of Cambridge and co-director of the Centre for Protein Misfolding Diseases.
Professor Knowles said: “It is a common problem in a range of areas of great practical importance to have active molecules that possess beneficial properties but are challenging to stabilise for storage.
“A conceptually simple, but powerful, solution is to put these inside tiny capsules. Such capsules are typically made from synthetic polymers, which can have a number of drawbacks, and we have recently been exploring the use of fully natural materials for this purpose. We are particularly excited by the potential to replace plastics with sustainable biological materials for this purpose.”
Dr. Ulyana Shimanovich, who performed a major part of the experimental work as a St John’s College Post-Doctoral research associate, and now works at the Weizmann Institute of Science, said: “Silk is a fantastic example of a natural structural material but we had to overcome the challenge of controlling the silk to the extent that we could mould it to our designs which are more than a factor of a thousand smaller than the natural silk cocoons.”
According to the team, making conventional synthetic capsules can be difficult to achieve in an environmentally-friendly manner using biodegradable and biocompatible materials. Silk is not only easier to produce; it is also biodegradable and requires less energy to manufacture.
Silk micro-cocoons could also expand the range and shelf-life of proteins and molecules available for pharmaceutical use. Because the technology can preserve antibodies, which would otherwise degrade, in cocoons with walls that can be designed to dissolve over time, it could enable the development of new treatments for cancer, or neurodegenerative conditions.
The study was carried out with the support of the Cambridge Centre for Misfolding Diseases, whose research programme is focused on the search for ways of preventing and treating neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases.
Michele Vendruscolo, co-director of the Cambridge Centre of Misfolding diseases, said. “Some of the most efficacious and largest selling therapeutics are antibodies.” However, antibodies tend to be prone to aggregation at the high concentrations needed for delivery, which means that they are often written off for use in treatments, or have to be engineered to promote stability.”
Professor Knowles said: “By containing such antibodies in micrococoons, as we did here, we could significantly extend not just their longevity, but also the range of antibodies at our disposal. We are very excited by the possibilities of using the power of microfluidics to generate entirely new types of artificial materials from fully natural proteins.“
