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Plant a seed and, if the conditions are right, the seed grows. The process seems simple enough at first glance and is something many of us may feel like we learned in elementary school.

Neel Joshi, a Northeastern University associate professor of chemistry and chemical biology, says that the mechanisms are deeply complex. "To form something that's not just a ball of cells, but has a front and a back and a top and a bottom, all those things are pretty complicated. How it limits itself, it doesn't overgrow or undergrow. These are really difficult questions."

In research recently in the Proceedings of the National Academy of Sciences, Joshi and Ph.D. student Rong Chang modified E. coli bacteria to attach to one another in novel ways, using so-called disordered proteins to act like filaments, or fine hairs, to bind one cell to another.

Chang notes that by changing the environmental conditions around their modified E. coli—that is, changing the buffer material the E. coli resides in—the experimenters could "achieve reversible cellular organization."

In other words, the researchers could coerce the cells to adopt a particular shape, have them take a new, second shape, and then reverse the process, returning the cells to their earlier formation.

These results, according to Chang, "have never been reported before."

From scaffolding to direct contact

Joshi says that one of the primary goals in the engineering of living materials "is to be able to build structure like biology." In Joshi's lab, scientists engineer living cells to do things they've never done before.

That is, the researchers want to encode their own instructions into cells to get them to do what the researchers want. "We're trying to teach them a trick that they're not used to, and it's counter to some of their evolutionarily encoded programs," Joshi says.

Someday, Joshi says, he hopes to be able to "grow materials, like you grow a tree to get wood." When the cells are done growing, "you can harvest it, and you benefit from all of that bottom-up self-assembly that the cells do."

Plant cells, however, have the benefit of additional scaffolding in the form of polymers like cellulose, which provide the plant with rigidity and other properties, Joshi says. Joshi and Chang are interested in manipulating something more difficult: direct cell-to-cell contact.

Structures created through direct cell-to-cell contact are still found in nature, Joshi says, in places like our gastrointestinal lining, but even our skin uses polymers like keratin to retain its shape.

The hard problem of engineering living matter

"If you think about any type of structure building in biology," Joshi says, from human embryos to seeds growing into trees, cells take their genetic instructions and multiply in a specific fashion.

This means that cells "have to coordinate their division. So a few cells turn into many cells. And then they also coordinate how they are oriented with respect to one another," he says. They also have to know where to stop growing, where to form edges and boundaries.

"It's a hard problem to tackle from an engineering perspective," Joshi says.

The scaffold structure of a plant's cells is "an easier thing to mimic," Joshi continues. Indeed, "previous work in our lab and other labs had focused more on making scaffolds," he notes.

Direct cell-to-cell contact is much harder—but Chang found a way, using what Joshi calls an "accessory protein," called CsgF, to serve as an anchor on the outside surface of an E. coli cell.

Useful shapes

CsgF had been a carryover from another project the lab has been running for years. "Rong found a way to take this thing that we were familiar with—but we didn't have anything useful to do with—and he turned it into something useful," Joshi says.

The disordered proteins Chang and Joshi use with E. coli "don't have a particular 3D shape," Joshi says. Instead, they attach to the surface of the cell, waving around like kelp in an underwater forest. When two cells near each other, the hairs "stick together like Velcro," Joshi says.

They call these proteins disordered as they have no particular locked-in shape. In contrast, ordered proteins might manifest as something like an antibody, which will present in a Y shape. This specific shape "is what allows it to recognize a specific antigen," Joshi says.

Chang says that the system he and Joshi have developed "is dynamic. We can control its organization and reorganization."

A jumping off point

Chang calls their discovery a platform from which they can make other useful discoveries—and materials—with their disordered proteins.

"Disordered proteins can also be applied to different functions," Chang continues, incorporating a protein's natural properties into the structure.

"Many anti-freezing proteins are disordered," he says. Including these proteins into an engineered cellular structure could mean materials better capable of being "stored in different environments, like very low temperatures or high temperatures."

"If we can apply these proteins into our system, we can help the cells grow in very tough environments or tough conditions," Chang says.

"This really broad compatibility with virtually any disordered sequence is something that you know other people can build on now that Rong has shown it's possible," Joshi concludes.

This story is republished courtesy of Northeastern Global News .