Hydrogel from spider silk discovered by accident

Breaking new ground 25. sep 2022 3 min Professor Anna Rising Written by Kristian Sjøgren

A newly discovered hydrogel made from spider silk has great potential within research in chemistry and biomedicine. It may be used to attempt to repair organs and as a new way of delivering precision medicine.

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Most major scientific discoveries result from years of research that eventually lead to a final scientific realisation that has the potential to change the world. However, this was not the case for a recent discovery by researchers at the Karolinska Institutet in Sweden.

The researchers were studying spider silk in the laboratory, which suddenly acted differently.

This led to the discovery of a spider silk hydrogel – a cross-linked hydrophilic polymer that does not dissolve in water. This accidental discovery holds great potential within chemistry and pharmacology.

“We discovered that spider silk proteins, which normally appear in a solution, can form a hydrogel when they are heated to body temperature. Because of the properties of the hydrogel and the fact that we can combine spider silk proteins with other proteins and attach them to the hydrogel, this can be useful in producing refined chemicals or inside the human body,” explains co-author Anna Rising, Professor, Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

The research has been published in Nature Communications.

Major discovery happened by accident

The discovery was made after the researchers in Anna Rising’s laboratory could not understand for several days why the needles that the researchers use to spin threads of spider silk kept clogging up.

The liquid spider silk protein is usually easily pressed out of the cannulas and then forms fibres that can be spun into threads for use in textiles and rope.

Anna Rising’s laboratory is researching methods to give the silk thread very useful properties for various industries.

On the days when everything went wrong in the lab, however, the cannulas kept getting clogged, and the researchers discovered that this was because a hydrogel had formed inside them.

PhD student Tina Arndt investigated the phenomenon and found that the needles had been too close to a lamp that had heated the spider silk, and that the heating was enough for them to form the hydrogel.

Forms hydrogel at 37°C

Instead of discarding the cannulas with hydrogel, Anna Rising decided to investigate what had actually happened to the spider silk proteins.

She found that the N-terminal domain of the protein, which normally helps to make the protein soluble, had changed character when it was heated to 37°C – human body temperature.

At 37°C, the N-terminal domain begins to form fibrils, and the fibrils turn the solution into a hydrogel.

Under normal conditions, the N-terminal domain ensures that the spider silk proteins do not clump together within the spider’s silk glands. The glands also contain salt, which additionally prevents clumping.

But at 37°C and outside the glands’ saline environment, everything is different.

“To begin with, it is inherently interesting that a protein that we can produce in very large quantities in bacteria and is good for keeping other proteins in solution completely changes its character and forms a hydrogel when heated to 37°C,” says Anna Rising.

Can bind proteins permanently to the hydrogel

The researchers in Anna Rising’s laboratory conducted various experiments to determine what the hydrogel of spider silk proteins can be used for.

They fused the spider web proteins with other proteins, including a green fluorescent protein and proteins involved in nucleotide metabolism.

These experiments showed that spider silk proteins could be fused with other proteins while the fusion proteins retained their ability to form the hydrogel and the fused proteins maintained their functionality.

Anna Rising can envision several different uses for a hydrogel with these special properties.

“The hydrogel can be used to quickly and simply bind active proteins, where they can be placed with high density in the network of fibrils of spider silk proteins. Such a hydrogel can be useful in producing refined chemicals,” explains Anna Rising.

Can be used in biomedicine

Another potential area of application is in biomedicine.

Previous animal experiments have shown that spider silk is harmless to implant in an organism, and it could therefore potentially be injected into people without having to worry about side-effects.

One can envision fusing the spider silk proteins with biomedical molecules that are locked up locally inside the body, after being injected and heated to body temperature – thereby localising the effect of the medicine by preventing it from being distributed all over the body.

The researchers have also carried out experiments showing that whole cells can be fixed in spider silk hydrogel.

These cells can potentially be used in medicine in two ways.

  • Spider silk hydrogel could be injected into living cells, and these living cells could become small factories that continually produce medicine inside the body. This may include insulin.
  • Another option is to attach cells to different places in the body with the aim of making them grow. This application can be used within tissue engineering: regenerating tissue in organs.

“There are many possibilities for using the spider silk hydrogel. We have many ideas, but we also hope that other researchers can see the potential and would like to collaborate on developing our discovery,” concludes Anna Rising.

Spidroin N-terminal domain forms amyloid-like fibril based hydrogels and provides a protein immobilization platform” has been published in Nature Communications. In 2019, the Novo Nordisk Foundation awarded a Postdoctoral Fellowship for Research Abroad in Bioscience and Basic Biomedicine to co-author Cagla Sahin.

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