Scientists Mixed Squid DNA With Human Cells to Control Their Transparency in 'Revolutionary' Study

Scientists have changed the degree of transparency of human cells in a laboratory, according to a study. It is hoped the technique, inspired by see-through sea creatures, will help us gain a deeper understanding of our biological processes.

Academics not involved in the study, published in the journal Nature Communications, described the findings to Newsweek as "revolutionary" and "remarkable."

The authors took their idea from cephalopods, which include octopuses, squids and cuttlefish. By changing how their skin transmits, absorbs and reflects light, some of these animals can camouflage themselves. They can even perform "literal vanishing acts," wrote the authors.

The female Doryteuthis opalescens squid, for instance, can turn a stripe on its mantle from almost transparent to opaque white. This trick is made possible by cells called leucophores. These contain proteins known as reflectins, which affects how light bounces off cells.

To conduct the study, Alon Gorodetsky of the Department of Chemical and Biomolecular Engineering at the University of California, Irvine, and colleagues genetically engineered human cells—which are relatively transparent—to express reflectin. They did this by taking the DNA of squid cells, which contain what is essentially a reflectin recipe, and mixed it with human kidney cells in a lab culture. A number of the cells took up the DNA, and used the genetic coding from the squid DNA to make reflectin.

The new reflectin proteins were found to group together in small clusters. When the scientists exposed the cells to salt, the reflectin proteins grouped together even tighter, creating structures big enough to reflect light. Tweaking the levels of salt was found to make the clusters group and ungroup, turning them from transparent to white and back again.

reflectin, nature,
An image showing the human cells containing reflectin. The darker red areas are where reflectin are causing more light to bounce off the cells. Nature Communications, Gorodetsky et al

Gorodetsky told Newsweek via email: "One of the most surprising aspects about the findings was that human cells could not only produce the protein but could also organize it in the same way as cephalopod skin cells. The similarity between the images obtained from our human cells and from cephalopod skin cells (leucophores) was quite exciting!"

The ability to make mammalian cells and tissues more transparent for imaging has proven invaluable for better understanding their organization in 3-D, said Gorodetsky. "Our now-demonstrated ability to engineer and tune the transparency of living human cells could complement these existing exciting efforts."

However, Gorodetsky said: "Although this study opens up a lot of possibilities, a great deal of work will be necessary to extend our methods to other cell types and ultimately even tissues. One of the key issues is the incomplete understanding of the structure of our squid protein."

Scientists who weren't involved in the study praised the team's work. Gabriel Popescu, professor in electrical and computer engineering at the University of Illinois at Urbana-Champaign, told Newsweek: "It is remarkable that the capacity of many cephalopods to change their optical appearance with respect to their environment was transferred to mammalian cells."

Popescu said the study may help scientists get over the obstacles they face when trying to create contrast between cells. This process has traditionally relied on stains or emissions from substances such as potentially toxic fluorescent dyes, which doesn't work well with many mammalian cells.

"This study is likely to open up a new window into the function of cells, without the limitations associated with fluorescence," said Popescu.

"Tuning the transparency of cellular systems has tremendous potential," Popescu said. "For example, the main limitation in imaging deep into tissues stems from the strong scattering rather than absorption of light.

"Engineering the cells to reduce scattering provides essentially a 'clearer' window into the tissue function." This approach could also be used to investigate live cells, and may be helpful in a range of fields from tissue engineering to modeling cancer in labs and disease treatment, he said.

Dan Morse, distinguished professor of molecular, cellular and developmental biology at the University of California, Santa Barbara, told Newsweek: "This is a truly revolutionary accomplishment."

The scientists have "opened the door to the long-envisioned opportunities for genetic and cellular engineering of tunable biophotonics for future research," he said.

"The most immediate usefulness of this research is the development of a new method to probe the inner workings of cells, and the role of proteins inside them. The cells are initially pretty transparent already, so this method makes it possible to make them reflective and thus stand out in response to a signal."

However, Morse said the study was limited because each batch of cells needs to be treated with DNA and exposed to different levels of salt. But it may be possible to genetically engineer cells so their descendants inherit the reflectin gene. It may also be possible to make the cells reflect different colors, he said.

Professor Konstantin Lukyanov, head of the biophotonics lab at Russia's Skolkovo Institute of Science and Technology, told Newsweek: "To the best of my knowledge, this is the first example of functional expression of a reflectin in mammalian cells. This tells us that reflectin alone, being expressed in cytoplasm [a solution in cells] with no assistance of other specific proteins from the squid, can form optically-active structures."

Lukyanov said there were two limitations of using the technique to tag cells. Firstly, big reflectin granules change the structure of the cell, which while acceptable in this study could damage some cells such as neurons, and could "strongly affect more complex models such as embryos and cell organoids."

"Second, the difference in optical properties of cells with and without reflectin is rather small; it can be detected in a cell monolayer but most probably not in real biological systems where cell labeling is desirable," said Lukyanov.

This article has been updated with comment from Alon Gorodetsky.