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 solution 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 Communication Nature.
“We have developed a completely new method to create a three-dimensional gel from spider silk that can be engineered to deliver different functional proteins,” says Anna Rising, research group leader at the Department of Biosciences and Nutrition, Karolinska Institutet (KI) and Professor in 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 solution
In the future, the researchers hope to develop an 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 with enzymes, a form of protein used to speed up various chemical processes.
“In a bit longer term, I think injectable gels can become very useful in regenerative medicine,” says the study’s first author, Tina Arndt, a doctoral student in Anna Rising’s research group at Karolinska Institutet. “We have a long way to go, but the fact that the protein solution quickly forms a gel at body temperature and that the spider silk has been shown to be well tolerated by the body is promising.”
Mimics the spinning of spider silk
The ability of spiders to weave incredibly strong fibers from a solution of silk proteins 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 previously developed a method of producing valuable proteins that mimics the process the spider uses 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 applications,” says Anna Rising. “We let the bacteria produce that part of the protein bound to functional proteins, including various drugs and enzymes.”
Turned into gel
The new study shows that the N-terminal domain also has the ability to change shape into small fibrils that cause the protein solution to convert into a gel if incubated at 37°C. Moreover, it can be fused to functional proteins which retain their function in the gel.
The research was funded by the European Research Council (ERC), Center for Innovative Medicine (CIMED) at Karolinska Institutet and Stockholm Region, Stem Cell and Regenerative Medicine Strategic Research Area at 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.
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