Genome dynamics defy disruption in microgravity

Mechanical stress on human cells can alter the genome’s essential functionality, including how DNA is replicated and repaired. Directly poking a cell’s nucleus, for example, elicits these changes. But how our cells are affected by the most ubiquitous source of mechanical stress—gravity—has remained a mystery, largely because our bodies are constantly under its influence.

Alexandra Zidovska of New York University and colleagues set out to shed light on the role of gravity in the genome by studying how a cell behaves in its absence. ¹ They observed that although a lack of gravity appears to have a strong impact on the nucleus’s shape and size, the genome’s overall organization and dynamics inside the nucleus remain unchanged.

Rather than turning to orbital or parabolic flights or to drop towers to create a simulated microgravity environment, the team placed cell samples inside an apparatus called a random positioning machine, which rotates the samples in three dimensions, as shown in the video below, to effectively average away the influence of gravity.

But the rotation introduces a new problem: Forces from flows induced in the cells’ culture medium are difficult to separate from the effects of gravity. To account for that factor, the team designed a rotation algorithm that ensures even distribution of the cell samples’ orientation across all directions in a manner that both creates a simulated microgravity environment and produces essentially negligible flow. The new rotation scheme solves a decades-long problem in simulated microgravity experiments, Zidovska says.

The team studied cell samples in their optimized microgravity environment for 24-hour periods and imaged the nucleus (as seen in the figure) and the genome organization and dynamics in real time. The researchers observed that in the simulated microgravity, the nucleus changed shape and grew larger, suggesting gravity may play a role in holding its shape under normal Earth forces. Liquid phases in the nucleus, such as the nucleolus, also appear visibly affected by a lack of buoyancy and convection in the cell’s fluid nucleoplasm.

Despite those changes to the nucleus morphology, the organization and dynamics of the cell’s genome were unaffected. The result was surprising, the researchers say. Previous experiments have shown that mechanical stress can alter a genome by disrupting its coherent movement of genetic material, but the live-cell imaging in this new work shows that coordinated motion inside the genome was undisturbed in simulated microgravity.

A next step for the team will be to expose the cells to simulated microgravity for longer durations to see whether new effects emerge.