Gravity leaves the human genome largely unfazed, microgravity simulator reveals

Gravity is the one force that no organism on Earth can escape. It presses on every cell, every molecule, every strand of DNA, ceaselessly and without pause. Yet despite its omnipresence, scientists have had remarkably little to say about what gravity actually does to the genetic material inside our cells. A new study from New York University, published in Science Advances, takes a direct swing at that question by doing something deceptively simple: switching gravity off, at least in simulation, and watching what happens to the human genome in living cells.

The research, led by Alexandra Zidovska, an associate professor in NYU’s Department of Physics, addresses a gap that has persisted since the completion of the Human Genome Project. That monumental effort, launched in 1990 after decades of genetic breakthroughs, delivered a sequence of the human genome, but the physical rules governing how that genome is organized inside the cell nucleus remain an active and unsettled area of research. Among the unanswered questions is the role of gravity, a constant mechanical stress on everything that lives. To probe it, Zidovska and her colleagues reasoned, gravity must be removed as a factor, which is precisely what their custom-built laboratory apparatus was designed to do.

The stakes of the question are considerable. The human genome is a one-dimensional sequence encoded in roughly two meters of DNA molecules, packed with extraordinary efficiency into three dimensions inside a cell nucleus barely 10 micrometers across, about the width of a silk fiber. This compact hierarchical structure is directly linked to genomic function, and deviations from it can contribute to human diseases, including cancer, as well as developmental afflictions. But the physical principles that maintain this organization are not well understood, and it has remained unknown whether gravity contributes to preserving it, or whether its absence might induce genomic aberrations.

To find out, the NYU team designed and built a random positioning machine tailored for imaging the human genome in live cells. The device rotates dishes of living cells along two independent axes, following a three-dimensional rotational path that averages out the direction of the gravitational vector, producing a simulated microgravity, a condition of weightlessness created on Earth. The principle resembles that of the larger machines astronauts use in their training. A crucial preparatory step was the elimination of air bubbles from the cell cultures, since even small bubbles can interfere with delicate measurements during rotation.

Rotation alone, however, introduces a confounding problem. Turning a dish of cells through three dimensions inevitably stirs the surrounding fluid, generating flows that do not exist in genuine zero gravity outside Earth. Previous studies of simulated microgravity have often been obscured by such flows and by the cell aggregates they can induce. The researchers therefore developed novel 3D rotational algorithms that not only simulated microgravity but minimized fluid flow generation, and they created additional algorithms to investigate, separately, what flows themselves do to cells and their genomes. Together, these advances sharply reduced both fluid motions and cell clumping, allowing the team to isolate the effects of weightlessness from the artifacts of the simulation.

The experimental design then became a matter of careful comparison. The scientists exposed one set of cells to simulated microgravity with minimized flows, another to strong fluid flows, and a control group to neither condition, each exposure lasting 24 hours. They then deployed sophisticated imaging techniques, recording streams of images for detailed physical analysis. The measurements tracked changes in cell shape and volume, the shape and volume of the cell nucleus, the nuclear envelope, the genome itself, and the nucleolus, the largest liquid condensate within the nucleus. The team specifically examined changes in the genome’s organization and dynamics, as well as any DNA damage induced by the simulated conditions.

The results paint a picture of remarkable resilience, with telling exceptions. Cells exposed to flows became elongated in shape, but cells in simulated microgravity kept their form. The volume of the cell nucleus increased after exposure to weightlessness, indicating that on Earth gravity normally acts to diminish it. Despite that change in volume, the thickness and structure of the nuclear envelope, the membrane that encases the genome, remained unchanged, suggesting gravity has minimal influence on those architectural traits. Most strikingly, the genome itself maintained its physiological organization and motions throughout the day-long exposure to simulated microgravity, and the technique produced no detectable DNA damage, whereas exposure to flows did damage DNA. The nucleolus became smoother after exposure to either condition.

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 observed. In the same way, she noted, the results suggest that the physical organization of the human genome may undergo minimal changes in outer space during comparable timescales. The subtlety of the changes, however, comes with a caveat that the researchers themselves emphasize: small perturbations could amplify over time and eventually affect cell physiology, and longer exposures, particularly in the space environment where actual DNA damage occurs, could produce effects not seen in a single day of simulation.

The findings arrive at a moment of renewed ambition in human spaceflight, with plans for extended missions to the Moon and Mars raising urgent questions about how the body copes with weightlessness. How will the human genome be affected in outer space, Zidovska asked in describing the motivation for the work. By demonstrating that the genome’s organization and dynamics withstand a day of weightlessness on Earth, the study offers reassurance for short-duration exposures while framing the longer-term questions that future experiments, and future astronauts, will need to answer. It also provides the scientific community with a validated toolkit, combining imaging-compatible microgravity simulation with flow-suppressing algorithms, for disentangling gravitational effects from mechanical artifacts in cell biology.

Beyond its implications for space travel, the work speaks to a more fundamental mystery: the physics of the genome. Understanding which external forces shape, or fail to shape, the two meters of DNA coiled inside each of our cells touches on questions of disease, development, and the basic mechanics of life. The paper’s co-authors included Nikitas Kanellakopoulos, a doctoral student at NYU; undergraduates Manav Patel, Brandon Sato, and Melaina Lawrence; and Leif Ristroph, an associate professor at NYU’s Courant Institute School of Mathematics, Computing, and Data Science. The research was supported in part by grants from the National Science Foundation and the National Institutes of Health. For now, the message is one of quiet stability: the architecture of our genetic material, refined over billions of years, appears built to hold its shape whether it rests on Earth or floats among the stars, at least for a day.

Subject of Research: The effects of simulated microgravity and fluid flows on the organization, dynamics, and integrity of the human genome in living cells

Article Title: Scientists uncover gravity’s impact on the human genome

Article References: Scientists uncover gravity’s impact on the human genome. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: microgravity, human genome, cell nucleus, chromatin, DNA damage, nuclear envelope, nucleolus, random positioning machine, space biology, biophysics, Science Advances, New York University