Unraveling the biochemistry of spider silk.

Unraveling the biochemistry of spider silk

When the Greek maiden Arachne defeated Athena in a weaving contest, the jealous goddess turned the mortal weaver into a spider. Today, scientists envy silk-spinning arachnids for their molecular handiwork and the strong biological polymer they produce. Spiders use various types of silk for building webs, descending from heights, protecting their eggs or immobilizing their prey; scientists would like to create their own versions for uses such as artificial tendons, sutures and bulletproof vests.

Two molecular biologists unveil some biochemical secrets of spider silk in the September PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol. 87, No. 18). Randolph V. Lewis and Ming Xu at the University of Wyoming in Laramie have determined part of the amino acid sequence of the protein molecules that twine into dragline (major ampullate) silk of the orb-web spider Nephila clavipes. With its rubber-like springiness and its ability to suspend weights that would snap equivalent strands of steel, this silk has "nearly unmatched . . . strength and elasticity," the researchers note.

Uncovering the silk protein's structure stretches biochemists' skills. "It's an extremely difficult protein to work with," says Joseph Cappello of Protein Polymer Technologies, Inc., in San Diego.

"Mother Nature has taken millions of years to design a superior product," adds Harvey W. Keene of the U.S. Army Research Development & Engineering Center in Natick, Mass., where scientists are sequencing the dragline protein in search of lighter and stronger materials for bulletproof vests.

All proteins are made of amino acids, variously linked into unique chains. But silk protein's toughness keeps it from dissolving readily and makes it resistant to the protein-slicing enzymes used in standard sequencing methods.

Lewis and Xu deployed heavy-duty solvents to untangle and dissolve the silk's meshed protein molecules and used hot, concentrated acid to chop them into fragments. Using genetic engineering techniques, they then reversed the normal cellular routine in which a gene made of DNA gets transcribed into messenger RNA (mRNA) molecules, which then get translated into protein molecules. Instead, they used silk protein fragments to make DNA probes, which served as homing molecules for locating mRNA molecules in the spider's silk-making glands. The mRNA molecules in turn served as templates for reconstructing roughly one-third of the gene for the silk protein.

The amino acid pattern corresponding to the partial gene might help explain silk's properties, Lewis says. It consists of repeating units up to 34 amino acids long, each divided into three segments. Each unit's longest segment contains a nearly identical sequence of 15 amino acids, which arrange into the so-called beta sheets that give the molecule its strength. Another segment includes a string made only of the amino acid alanine. Its ability to form a springy helix probably endows the protein with elasticity. The remaining segment has a more variable sequence, making its functional role more difficult to surmise, Lewis says. The silk protein of silkworms, in contrast, consists of rigidly repeated units.

The next steps awaiting silk researchers include sequencing the rest of the dragline protein and other fibrous arachnid proteins such as those making up the swathing silk that spiders use to keep their victims from leaving before dinner.