Researchers from Karolinska Institutet in Sweden and the Swedish University of Agricultural Sciences have found that spider silk proteins can be fused to biologically active proteins and converted into a gel at body temperature. One of the goals is to develop an injectable protein option that forms a gel inside the body, which could be used in tissue engineering and for drug delivery, but also to make gels that can streamline chemical processes where enzymes are used. The study is published in Character Communications.
“We have developed an entirely new method to create a three-dimensional gel from spider silk that can be engineered to provide different functional proteins,” says Anna Climbing, Research Group Leader at the Department of Biosciences and Nutrition, Karolinska Institutet (KI) and Professor at the Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences (SLU). “The proteins in the gel are very close to each other and the method is so gentle that it can be used even for sensitive proteins.”
An injectable protein option
In the future, researchers hope to develop a injectable protein solution that forms a gel inside the body. The ability to design hydrogels with specific functions opens up a range of possible applications. Such a gel could, for example, be used to obtain a controlled release of drugs in the body. In the chemical industry, it could be fused to enzymes, a form of protein used to speed up various chemical processes. Injectable gels can become very useful in regenerative medicine,” says the study’s first author, Tina Arndt, a PhD student in Anna Increasing’s research group at Karolinska Institutet. “We have a long way to go, but the fact that the protein solution forms a gel quickly at body temperature and the spider silk has been shown to be well tolerated by the body is promising.”
Imitates spinning spider silk
The ability of spiders to weave incredibly strong fibers from a silk protein option in fractions of a second has sparked interest in the underlying molecular mechanisms. The KI and SLU researchers were particularly interested in the ability of spiders to keep proteins soluble so they don’t clump together before spinning spider silk. They have previously developed a method of producing valuable proteins that mimics the process used by the spider to produce and store its silk proteins.
“We have already shown that a specific part of spider silk protein called the N-terminal domain is produced in large quantities and can keep other proteins soluble, and we can exploit it for medical purposes,” says Anna Mounting. “We let the bacteria produce that part of the protein bound to functional proteins, including various drugs and enzymes.”
Transformed into a gel
The new study shows that the N-terminal domain also has the ability to change shape and change into small fibrils which cause the protein remedy to convert into a gel if incubated at 37°C. In addition, it can be fused to functional proteins that retain their function in the gel.
The research was funded by the European Research Council (ERC), the Center for Innovative Medicine (CIMED) at the Karolinska Institutet and the Region of Stockholm, the Strategic Cell Research Area Stem and Regenerative Medicine from the Karolinska Institutet, the Swedish Research Council, the European Regional Development Fund and the Novo Nordisk Foundation. The study was also conducted using the central Biomedicum Imaging Core (BIC) facility at Karolinska Institutet. The researchers affirm that there are no conflicts of interest.