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Internet of Cells: The Next Revolution?

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Cells are the fundamental units of biology. They have long seemed like individuals. Sure, they communicate, like humans, and they build structures together, sharing the work with division of labor. But like factory workers going home at the end of the day, cells can be treated as independent units with their own lives to live. To evolutionary biologists, cells divide alone and evolve independently. Isn’t that one of the basic premises of modern biological science?

Take heed: the next biological revolution is coming. Nature calls it “The Internet of Cells” and says that it has biologists buzzing.

The revolution began, Monya Baker writes, when biologists noticed that proteins engineered to appear in certain cells appeared to have “teleported” to a different group of cells entirely. Then came the discovery of molecular nanotubes that appear to transmit genetic information and even organelles between cells. Gradually, cells seemed to be losing their independence.

Yamashita’s tubes joined a growing catalogue of cryptic conduits between cells. Longer tubes, reported in mammalian cells, seem to transport not just molecular signals but much larger cargo, such as viral particles, prions or even mitochondria, the cell’s energy-generating structures. These observations suggest an unanticipated level of connectivity between cells, says Amin Rustom, a neurobiologist at the University of Heidelberg in Germany, who first spotted such tubes as a graduate student almost 20 years ago. If correct, he says, “it would change everything in medical applications and biology, because it would change how we see tissues”. [Emphasis added.]

A short video clip reveals what appear to be “interstate highways” reaching out and connecting between cells, passing material between them. The concept of intercellular trafficking through conduits is controversial, because no one knows exactly what is being transported and how often this occurs. The nanotubes, a mere 200 nm in diameter (wide enough to transport protein scraps), have been observed in the lab, but not as clearly in living organisms. They are hard to see. What are they doing?

Baker recounts lab findings in 2004 that showed “something even more radical: nanotubes in mammalian cells that seemed to move cargo such as organelles and vesicles back and forth.” Since then, more “membrane nanotubes” have been found.

Meanwhile, other labs have reported cell-connecting tubes in neurons, epithelial cells, mesenchymal stem cells, several sorts of immune cell and multiple cancers. Further types of tube have been spotted as well. In 2010, Gerdes and his team reported that some tubes end in gap junctions: gateways that bestow the neuron-like ability to send electrical signals and can also pass along peptides and RNA molecules.

The “internet of cells” might also explain how disease agents, such as viruses, spread among tissue cells, or how cancer cells hijack their neighbors. Not everyone is jumping aboard the new paradigm, because the implications are huge. Eliseo Eugenin at Rutgers Medical School

thinks that other researchers are sceptical of nanotubes because they are unable to reconcile themselves to the idea that cells are constantly exchanging materials, including genetic information. “Our definition of a cell is falling apart,” Eugenin says. “That is why people don’t believe in these tubes, because we have to change the definition of a cell.”

The race is on to convince skeptics with better imaging of functional transport within multicellular organisms. Baker doesn’t say much about evolution. She notes that one researcher speculated, “Membrane protrusions might have evolved first, and higher organisms could have started upgrading them to make neurons for more complicated functions.” Such personification language is not particularly helpful for materialists. Baker quickly pivots and says, “Most researchers who study these cellular pipelines care less about their evolutionary origin than about their role in human health and disease.” As such, the “internet of cells” looks like it will be a boon for design research, and a challenge to Darwinian evolution.

Sharing Genetic Information

A separate paper in PNAS discusses “Intercellular mRNA trafficking via membrane nanotube-like extensions in mammalian cells.” Notice how this team of Americans and Israelis describes the finding as a revolutionary development in biology:

mRNA molecules convey genetic information within cells, beginning from genes in the nucleus to ribosomes in the cell body, where they are translated into proteins. Here we show a mode of transferring genetic information from one cell to another. Contrary to previous publications suggesting that mRNAs transfer via extracellular vesicles, we provide visual and quantitative data showing that mRNAs transfer via membrane nanotubes and direct cell-to-cell contact. We predict that this process has a major role in regulating local cellular environments with respect to tissue development and maintenance and cellular responses to stress, interactions with parasites, tissue transplants, and the tumor microenvironment.

The team admits that “The biological importance of mRNA transfer between cells is still unknown,” but the concept of sharing of genetic information between cells appears to overturn long-held assumptions about the independence of cells.

As for what cells are sharing, many possibilities come to mind. For instance, “the transfer of mRNAs involved in cell differentiation during embryonic development might act as means to induce or repress neighboring cells.” Conceptualizing the rapid transfer of genetic information via “nanotubular highways” between cells opens up many new avenues for research. “Determining the scope of this process and deciphering the mechanism and physiological outcome of mRNA transfer will be the goal of future studies,” they conclude.

More Evidence

Hormones and signal molecules have long been known to travel between cells, but direct transport by contact is fairly new. Science Daily reported on work at Vanderbilt to learn how cells communicate during wound healing. The cell’s signals are “surprisingly complex”, the headline says. One hypothesis had been that cells send proteins to their neighbors that trigger them to boost their calcium levels.

The second hypothesis proposes that the trigger signal spreads from cell to cell through gap junctions, specialized intercellular connections that directly link two cells at points where they touch. These are microscopic gates that allow neighboring cells to exchange ions, molecules and electrical impulses quickly and directly.

“What is extremely exciting is that we found evidence that cells use both mechanisms,” said Shannon. “It turns out cells have a number of different ways to signal injury. This may allow them to differentiate between different kinds of wounds.”

Implications for Design Research

Darwinian theory presupposes some kind of “unit of selection” in biology. Evolutionists have long debated whether the unit of selection is a gene, a cell, an organism, or (less commonly proposed) a population of organisms. Neo-Darwinism has long focused on cells as units of selection, because that’s where genetic mutations take place that might be beneficial. Essential to the theory, though, is some degree of independence of the unit of selection, so that whatever beneficial variation appears can be victorious in the struggle for existence.

If organisms routinely share their information, however, all evolutionary bets are off. There won’t be competition if all the players share the benefit. We saw this conundrum when evidence grew for rampant horizontal gene transfer between microbes, and then between higher organisms. Some biologists considered the existence of a “quasi-species” in which a population could rapidly recover from individual stresses because of information sharing.

The “internet of cells” bears more similarity to “cloud computing” than to classical notions of Darwinian evolution. If functional information is routinely shared throughout the internet of cells, that looks a lot more like cooperation than competition. Prospects for research in this hot new paradigm appear wide open for non-Darwinian interpretations.