Researchers at the Karolinska Institutet in Sweden and the Swedish University of Agricultural Sciences have discovered that spider silk proteins can be fused with biologically active proteins and turned into a gel at body temperature.
One goal is to develop an injectable protein solution that forms a gel inside the body that can be used in tissue engineering and drug delivery, but also to make gels that can optimize the chemical processes by which they use enzymes. The research is published in Nature Communications.
“We have developed a completely new method to create a three-dimensional spider web gel that can be engineered to deliver different functional proteins,” said Anna Reising, head of a research group in the Department of Biosciences and Nutrition, Karolinska Institutet and professor in the Department of Anatomy. physiology and biochemistry, Swedish University of Agricultural Sciences.
“The proteins in the gel are very close together and the method is so mild that it can be used even for sensitive proteins.”
Injectable protein
In the future, researchers hope to develop an injectable protein solution that forms a gel in the body. The ability to design hydrogels with specific functions opens up a wide range of possible applications. Such a gel can for example be used to achieve a controlled release of drugs in the body. In the chemical industry, it can be fused with enzymes, a form of protein used to speed up various chemical processes.
“In the slightly longer term, I think injectable gels could become very useful in regenerative medicine,” said study first author Tina Arndt, a PhD student in Rising’s research group at Karolinska Institutet.
“We have a long way to go, but the fact that the protein solution rapidly gels at body temperature and that spider silk has been shown to be well tolerated by the body is promising.”
The ability of spiders to spin incredibly strong fibers from a silk protein solution in fractions of a second has sparked interest in the underlying molecular mechanisms. The researchers were particularly interested in the spiders’ ability to keep proteins soluble so they don’t stick together before spinning the web.
Shapeshifting ability
Scientists have previously developed a method to produce the valuable protein that mimics the process used by the spider to produce and store its silk proteins.
“We previously showed that a specific part of the spider silk protein, called the N-terminal domain, is produced in large quantities and can keep other proteins soluble, and we can use this for medical applications,” Rising said.
“We let the bacteria produce this part of the protein, which is linked to functional proteins, including various drugs and enzymes.”
The new study shows that the N-terminal domain also has the ability to change shape and switch to small fibrils that cause the protein solution to turn into a gel if incubated at 37°C. Also, it can be fused to functional proteins that retain their function in the gel.
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