Scientists Simulated Microgravity in Human Cells and Found Something Unexpected About DNA

Simulated microgravity changed the nucleus but left the genome surprisingly intact.

Every cell in your body has spent its entire existence under gravity’s pull.

Inside each of them, roughly two meters of DNA must fit inside a nucleus only about 10 micrometers across. Those two meters are folded with proteins into chromatin, a carefully organized three-dimensional structure whose arrangement helps govern which genes cells can use.

So what happens when “down” effectively disappears?

In a new study, researchers at New York University subjected living human cells to 24 hours of simulated microgravity and watched their nuclei and genomes respond. The nucleus grew larger and some structures inside it subtly changed. Yet the DNA packed inside remained remarkably stable. Its overall organization changed very little, and the chromatin showed no meaningful change in the subtle movements it normally makes within the nucleus.

Even more unexpectedly, the simulated microgravity did not measurably increase serious DNA damage. But when the researchers exposed cells to the fluid currents generated by the rotating apparatus, signs of DNA double-strand breaks rose significantly.

“On Earth, the role of gravity is intriguing—it is a constant mechanical stress on everything,” Alexandra Zidovska, a physicist at NYU who led the study, said in a university release. “We wanted to know what gravity’s role is in the genome’s organization and function here on Earth.”

Removing a Grounding Variable

So how does one turn gravity off?

Zidovska and her colleagues built a device called a random positioning machine. It continuously rotates dishes of living cells around two axes, repeatedly changing their orientation relative to Earth’s gravitational field. Over time, the cells experience an averaged-out gravitational direction—a laboratory approximation of microgravity.

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But this motion creates another problem: it moves the liquid surrounding the cells.

Flowing liquid exerts shear forces. A 2023 study of clinorotation experiments found that an apparent microgravity effect on developing muscle cells—they were less able to fuse together and form mature, multinucleated muscle fibers—was actually caused by fluid motion. The NYU team therefore designed a rotation pattern specifically to minimize these currents and separately exposed other cells to strong flow.

They used fluorescently labeled HeLa cells so they could watch chromatin, the nuclear envelope, and markers of DNA damage in living cells immediately after treatment. Previous microgravity experiments often relied on cells fixed after the experiment, making their internal dynamics harder to reconstruct.

After 24 hours, the nuclei exposed to simulated microgravity increased in area by about 14% and in volume by about 18%. Yet the membrane surrounding the nucleus remained about as thick as before. The nucleolus—a dense, liquid-like compartment inside the nucleus involved in ribosome production—also became smoother.

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Yet the DNA inside proved less perturbed.

Measurements of chromatin density showed changes of less than 5%, while analyses tracking how chromatin moved through the nucleus found no significant changes in its speed or coordinated motion.

In other words, the container changed more than its contents.

One of Many Stresses

The sharpest contrast came when the researchers looked for double-strand breaks, among the more serious forms of DNA damage.

Cells exposed to simulated microgravity showed no statistically significant increase. Cells subjected to strong fluid flows, however, showed nearly 30% more DNA-break markers than static controls.

That finding may help untangle a long-standing problem in space biology.

Real astronauts experience many stresses simultaneously: microgravity, radiation, altered sleep, fluid shifts, and confinement, among others. NASA’s Twins Study found extensive changes in gene expression and signs associated with DNA damage during Scott Kelly’s year aboard the International Space Station. More recently, studies of the four-person Inspiration4 mission found changes in gene activity and chromatin accessibility after just three days in orbit.

Those studies show that spaceflight affects genome biology. But they cannot easily tell researchers which part of the space environment caused each change.

The new experiment tackles almost the opposite question by isolating one physical factor. Its answer, at least after one day in cultured cells, is somewhat reassuring: removing the usual gravitational cue altered the nucleus, but the genome’s physical architecture largely held its ground.

“Our data show that the genome, its organization, and dynamics are incredibly robust and seem unaffected by gravity, or lack thereof, after 24 hours,” Zidovska said in a statement.

There are important caveats. These were cancer-derived HeLa cells in simulated microgravity, not healthy tissues inside astronauts, and the researchers did not comprehensively measure gene expression. Twenty-four hours is also a tiny fraction of a months-long mission.

The subtle changes they observed could accumulate with time. But for now, the experiment suggests that when “down” disappears, the genome may be one of the cell’s more stubborn structures.

The study was published in the journal Science Advances.