Artist's conception of computer-designed protein units starting to self-assemble for forming filaments. Source: Institute for Protein DesignNewly developed, self-assembling protein filaments could lead to the construction of entirely novel materials unlike any found in nature.

In the natural world, protein filaments are used in the cytoskeletons that give cells their shape; the cellular microtubules that orchestrate cell division; and in collagen, which gives both strength and flexibility to cartilage, skin and other tissues. The new filaments, which are designed and built from scratch, are constructed from identical protein subunits that snap together spontaneously to form long, helical, thread-like structures.

They were developed by a team led by David Baker, a professor of biochemistry at the University of Washington School of Medicine. Baker said that the ability to create the filaments from scratch will generate a better understanding of the structure and mechanics of naturally occurring protein filaments, along with allowing the creation of entirely new materials. These might include man-made fibers that equal or surpass the strength of spider silk — a structure that, by weight, is stronger than steel. Nanoscale wire circuitry is another possibility.

To design the filaments, researchers made use of a computer program developed in the Baker laboratory, called Rosetta, that can predict the shape of a protein from its amino acid sequence. Proteins must fold into a precise shape to function properly; that process is driven by amino acid properties and interactions with each other and the surrounding fluid environment. Forces of attraction and repulsion drive the protein to come to rest in a shape with the lowest energy level. By calculating energy levels, Rosetta can predict what that shape will be — with a high degree of accuracy.

The program was able to guide the team to design small proteins with amino acids on their surface that would cause them to latch into one another. This allowed the creation of a helix assembly, with amino acids aligned like steps in a winding staircase. Stability was added by binding copies of the proteins above and below themselves as the helix winds around, tier by tier. The proteins are relatively small, made up of around 180 to 200 amino acids and only about one nanometer long. Once assembled into stable filaments, however, they measure more than 10,000 nanometers in length.

"We were eventually able to design proteins that would snap together like Legos," said Hao Shen, a Ph.D. candidate at the UW Molecular Engineering & Sciences Institute. Tinkering with the designed protein's concentration in solution and by adding caps that inhibited its ability to bind also allowed the researchers to drive filament growth or disassembly.

"The stability of these proteins suggest they could serve as easily modifiable scaffolds for a range of applications — ranging from new diagnostic tests to nanoelectronics," Baker said.

The research appears in the Nov. 9, 2018, edition of the journal Science.