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CELL CULTURE'S SPIDER SILK ROAD
 
Jeffrey Perkel
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Silky Tissue

Nobody claims that every cell culture lab needs spider silk; its sweet spot seems to be tissue engineering. Spider silk can guide cell growth in vivo, produce a protective coating for implants, and serve as a matrix into which cells may be seeded in vitro, producing a material sturdy enough for implantation.

In general, says Wendy Bray, who manages the cell culture matrices portfolio at Thermo Fisher Scientific, researchers use three-dimensional cell culture matrices to mimic the cell's normal physiological niche. In the body, she explains, cells do not normally exist in two-dimensional sheets; they interact with other cells and receive a steady stream of signals from all sides. Some immortalized cell lines can grow without those cues, but studies have repeatedly documented differences in morphology, gene expression, and other behaviors from cells grown under more physiological conditions. Primary hepatocytes, for instance, will not grow well on standard culture dishes, Bray says; they prefer to be sandwiched between layers of collagen and murine extracellular matrix extract. “They need to be totally surrounded by that type of an environment in order to behave normally,” she says.

There's no shortage of commercial materials providing some of those features, including scaffolds, hanging drops, and hydrogels. What spider silk brings to the table is biocompatibility, biodegradability, tunable mechanical stability, and, at least for recombinant protein, a defined chemical composition. “It's perfect for 3D scaffolding,” says Fritz Vollrath, Professor of Zoology at Oxford University.

–J.P.

The most common silks are blank canvases, says David Kaplan, Professor and Chair of Biomedical Engineering at Tufts University. “They have very little specific cell-activating chemistries, which means you can use them as a nice scaffolding onto which you can add selectively other things as you wish.”

Kaplan, for instance, has modified silk proteins to nucleate glass and hydroxyapatite to make them stiffer. Hedhammar and Scheibel have independently coupled silk proteins to cell-adhesion moieties, such as the integrin-binding motif, RGD, to cause cells to bind the material more tightly. “If we stain the cells on spider silk compared to a [untreated] tissue culture plate, we can see that these adhesion sites are pronounced on the spider silk but not on the other. And that goes hand in hand with the proliferation—they grow better when they adhere in a natural way.”

Presumably, says Lewis—who has cultured Chinese hamster ovary, fibroblast, and retinal cells on silk protein— the material could be modified to attract or repel specific cell types to accelerate, for instance, healing processes in vivo.

Significant testing remains to be done before any such benefits come to pass. At the moment, researchers are still working out the basics of structure and function—why different silks have different properties. Should they unlock such secrets, and figure out how to exploit them, the bioprospectors could come a-running. Lewis, whose office in Utah features a “5 SILK” Wyoming vanity plate, has already staked his claim. But with nearly 45,000 documented spider species, there's still plenty of room for others.

References
1.) Sanggaard, K.W.. 2014. Spider genomes provide insight into composition and evolution of venom and silk. Nat Commun 5:3765.

2.) 2011..

3.) Kuhbier, J.W.. 2010. Interactions between spider silk and cells — NIH/3T3 fibroblasts seeded on miniature weaving frames. PLoS ONE 5:e12032.

4.) Wendt, H.. 2011. Artificial skin — Culturing of different skin cell lines for generating an ar tifical skin substitute on cross-weaved spider silk fibres. PLoS ONE 6:e21833.

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