Which is a major finding. Size, biologically, matters: The forces of nature are scale-dependent, which means that different forces become relevant—and essentially irrelevant—at different length scales. So the quantum effects that exert themselves on matter at microscopic scales average out as you move up to larger length scales. And gravity's force, in turn, becomes negligible at a certain smallness of scale. Biologists have long assumed that animal cells fall below that point—that they are simply too small to be affected by gravity. So while, at a tissue level, sure, cells are subject to gravity, at the level of the tiny individual, the thinking went, gravity wasn't one of the forces that cells are subject to. In microbiology, "we really have never, in my experience, worried about gravity—or thought about it," Brangwynne told me.
Brangwynne's work, published in Nature Cell Biology, may change that. And it may offer, as well, an answer to a longstanding mystery about where that line may be drawn: At what point, exactly, does gravity stop mattering to matter?
Brangwynne came to his findings with the help of some fairly ingenious technology. He also came to them somewhat unexpectedly. His previous work had shown that certain large particles within cells act essentially like water droplets, merging as they contact each other. In cells' nuclei, however, something seemed to be keeping them from fusing. To follow up on that observation, Brangwynne and his co-author, graduate student Marina Feric, studied egg cells of the African clawed frog, which are, like other eggs, anomalous in that they can reach sizes of 1 millimeter in diameter. The pair were studying, in particular, how the eggs are engineered: They wanted to explore why the nuclei of those larger cells contain, compared to smaller cells, a significantly higher concentration of actin, the protein that forms microfilaments in eukaryotes.
To do that, they turned to engineering of a more mechanical variety: microrheology, a technique that allows for the examination of viscosity within cells. They first tested whether the nuclei had a kind of mesh scaffolding that would allow smaller particles to move through the mesh but cause larger particles to get trapped—which would explain why those nuclei wouldn't fuse. Feric injected the frog egg nuclei with microscopic, Teflon-like beads of varying sizes. She then used microscopic imaging to observe the results. As she and Brangwynne predicted, the small beads diffused throughout the nucleus ("we watched them, basically, dance around," Brangwynne puts it) while the larger ones got stuck. A scaffold did, as they suspected, seem to be in place in the larger cells.
Feric then tested whether that scaffolding could be made up of actin. (Actin is known to form a kind cytoskeleton outside cells' nuclei, but its structural role in the nucleus has been largely unclear.) They treated the cells' nuclei with anti-actin drugs, disrupting their scaffolding stuctures. And when they did that, something more unexpected happened: The organelles that are naturally suspended throughout the nucleus of the cell ... fell. It was, as Brangwynne says, "exactly like what you would see if you took a marble and dropped it into a bucket—it's going to plop right down to the bottom."