Underneath the rubbery skin of a squid, you’ll find a community of cells and muscles that work together to create the color and texture changes these animals are known for. This buzzing cellular network is difficult to study, however, and marine biologists and other researchers failed to cultivate a squid’s skin cells in a laboratory setting for decades.
Now, thanks to recent work done at the University of California, Irvine, a workaround for culturing similar skin cells has been achieved.
How Squid Change Color
The researchers used genetic engineering, advanced 3D microscopy and computational modeling to generate and study human cell cultures with tunable transparency. They believe their engineered cells will shed light on how wild squids turn transparent — and potentially also offer new medical imaging methods.
Squids and octopuses rely on three different cell types within their skin to change color. “There are cells that reflect light with narrowband reflection called iridophores,” begins lead researcher and UC Irvine professor Alon Gorodetsky.
Iridophores reflect light at different wavelengths, and can change color depending on the angle of light. Previous research has found that when looked at from above, for example, an iridophore may appear blue — but from the side, it looks red.
Cephalopods also rely on tiny sacs of pigmented cells called chromatophores. “The colors are precisely layered, with yellow over red over brown,” says Leila Deravi, a professor at Northeastern University who was not involved in the study.
When a cephalopod decides to change color, it contracts or expands adjoining muscle cells to compress or open the chromatophore — changing its shape and how it reflects light.
But Gorodetsky and his team focused explicitly on the third type of cell, called leucophores, which scatter light. “They have broadband scattering across the visible spectrum,” he says.
When the cells reflect light, leucophores appear white. According to Shu Yang, a professor at the University of Pennsylvania, these types of cells are essential because they “provide white contrast” for the highly pigmented iridophores and chromatophores.
As a result, leucophores ensure a better color match to the environment, which is necessary for creating successful camouflage.
Read More: 4 Hidden Ways Animals Camouflage Themselves
Squid Changing Color Experiments
To create this white color, leucophores rely on particles from a specific protein called reflectin. Their assembly state — whether clustered or more separated — can cause cells to become more opaque or transparent, depending on the immediate surroundings.
To Gorodetsky and his team, the reflectin proteins seemed the perfect biomolecule for forming similar particles in mammalian (human) cells. Unfortunately, the COVID-19 pandemic broke just as the UC Irvine researchers were working on expressing these reflectin proteins.
Forced to work remotely, the scientists used various types of computational modeling and an advanced microscopy technique called holotomography to study the effects of reflectins in mammalian cells.
“We have gained a detailed understanding of the self-assembly of these nanoparticles inside cells using holotomography, which is a technique that allows you to visualize the cell in three dimensions,” Gorodetsky says. “And that gave us insight into the assembly state of these light-reflecting particles inside the cell and how that state can change.”
Once pandemic regulations eased off enough to return to the laboratory, the researchers used various other methods to confirm and reinforce their experiments.
The Evolution of Designer Cells
Gorodetsky and his team genetically engineered the self-assembling reflectin proteins in stable mammalian cells. They then tested the response of the nanostructures to changes in salt concentration in the surrounding environment, to mimic the habitat of cephalopods.
During these tests, the researchers found their cell cultures maintained high viability even when expressing large amounts of the reflectin proteins. In a saltier solution, as the reflectin proteins clumped together, the cells scattered more light and became more opaque.
“This is an incredible engineering advancement,” Deravi says, “being able to genetically engineer cephalopod-specific proteins and protein geometries in composition to mammalian cells. That means you can think about making designer cells with functions they weren’t originally evolved to do.”
In a recent press release, Gorodetsky explained that these developments could offer a way to study cells in real time without bleaching or hurting the sample. Additionally, in a media briefing held by the American Chemical Society, he mentioned potential advancements to medical imaging.
“This can be great for imaging live mammalian cells to see how they’re surviving,” Deravi says.
Invisible Camouflage: Not Ready for Humans
Squid camouflage continues to inspire both research and science fiction in tandem.
“H.G. Wells proposed that you could make The Invisible Man by matching the refractive index to the surroundings and eliminating all the pigments that give color,” Gorodetsky says.
Some science fiction characters even seem to mimic these mammalian cells expressing reflectin.
“There was an awesome scene in X-Men: Days of Future Past where they showed how Mystique’s skin cells would work,” Gorodetsky continues. “And it showed that they were filled with these little nanoparticles, which would change their assembly state or change the color.”
While Gorodetsky and his team did use human cells to culture the reflectin proteins, he emphasizes that the reflectin proteins are not yet ready for human subjects. In other words, we can’t create invisible men or Mystiques using this technology … yet.