Spider silk is a bit of a dream material, stronger than steel by some measures yet incredibly light and flexible. Obtaining spider silk, however, is a bit of a nightmare, as most spider species are both extremely territorial and prone to cannibalism. While we have managed to identify the genes that are needed to produce silk, inserting those into other species hasn’t worked out especially well, since silk formation depends on fairly precise mixtures of several proteins, as well as how the spider extrudes the fiber.
A Chinese group is now reporting some progress in overcoming at least some of these challenges. Their trick was to insert the genes into a domesticated species that already makes something like spider silk—specifically, the species that gave us the term silk. The new bit of genetic engineering has resulted in a silkworm that produces a hybrid silkworm/spider material that’s not as tough but is a bit stretchier than native spider silk.
More than meets the eye
If you’ve ever watched a spider spinning a web, silk production seems remarkably simple. But there’s enough going on there to make a materials scientist dizzy. Most spiders make more than one kind of silk, as the properties that might make a good web might not be the same as the ones that would effectively arrest a fall after a spider has leapt off a tree branch. The differences come in part because silk is composed of multiple proteins, and some spiders have genes for different versions of these proteins. If they have some control over which starting materials go into their silk, a spider species can adjust its properties.
But starting materials aren’t the only means to alter silk. The rate at which its extruded by the spider controls factors like the thickness of the silk, its water content, and how quickly it undergoes any reactions with oxygen. All of these can also influence the properties of the silk.
So making useful silk isn’t simply a matter of getting a single gene from a spider and sticking it in bacteria. The Chinese researchers decided to focus on finding a way to produce the silk in a spider-like environment, while avoiding the cannibalism issue. That led them to an insect we domesticated many centuries ago that also produces silk: the silkworm itself. While the original silk clearly has some different material properties than spider silk, there is some overlap, including a set of proteins with functional similarities.
They weren’t the first ones to try this; earlier attempts had been made to put spider genes in the silkworm. But these were based on a simple insertion of the gene from spiders, which turned out not to make much protein. The little that was made (typically five percent of the total silk or less) was also mixed in with the equivalent protein from the silkworm.
Editing in some spider
To get around these issues, the researchers decided to use gene editing. They designed proteins that would cut the silkworm’s chromosomes on either side of a gene that encodes a major silk protein. RNA encoding those proteins was injected into silkworm eggs, along with a DNA template that would allow the egg to repair the chromosome by inserting a spider silk gene instead. This put the spider gene under the control of the factors the silkworm normally uses to create silk proteins, which worked much better, as about 35 percent of the resulting silk was composed of the spider protein.
That’s not as good as the gene it replaced, which is normally about double that percentage of the silk fibers. But the spider gene is much smaller, so this wasn’t a direct one-to-one replacement of the gene. In fact, the researchers suspect that the silkworm had some trouble due to the differences between the spider protein and the one that it used to make, as the silk-producing glands had some defects in the engineered animals.
The silk itself was also slightly different, shrinking in diameter by about 16 percent. Its ability to withstand stress without breaking was down by a similar percentage. But there were some good features; the spider-silkworm hybrid silk could be stretched to about 1.5 times the length that normal silk could without breaking.
Overall, this appears to be a good first step. There are clear problems due to the mismatch between the spider protein and the silkworm version it replaces. It may be possible to engineer the spider protein to increase its size; a lot of its structure is composed of repeated variations of a string of amino acids, and it’s possible that the number of repeats could be expanded without causing problems. Alternatively, we can engineer more of the spider proteins into their silkworm equivalents, gradually transitioning the whole silk into something more spider-like. Whether that would allow silkworms to form cocoons (the normal purpose of the silk) isn’t clear, but that may not matter for the production of large amounts of spider silk.
, 2017. DOI: 10.1073/pnas.1806805115 (About DOIs).
