Cell Time

Human cell nuclei, with the nuclear membranes labeled in green and the nuclear contents labeled in purple.

Fang-Yi Chu and Alexandra Zidovska

The size and shape of human cells fluctuate slowly and predictably during different phases of the cell-division cycle. About four years ago, however, scientists noticed that in some cells, the boundary around the cell nucleus, called the nuclear membrane, also appears to oscillate in shape over much shorter periods of time. A new study has mapped the shape and timing of these rapid changes and concluded that they may serve as an internal clock for the cell.

Scientists Fang-Yi Chu, Shannon C. Haley, and Alexandra Zidovska, in the Department of Physics at New York University, fluorescently labeled the nuclear membrane and inner nuclear contents of cells derived from the Henrietta Lacks cell line. By tagging the nuclear membrane with one marker and its inner contents with another marker, they were able to precisely examine and record the shapes and contours of the cell nucleus. State-of-the-art spinning disk confocal microscopy—a technique that uses principles similar to those of a pinhole camera in order to improve image resolution—allowed the researchers to track changes in the cell nucleus over the time frame of seconds in living cells. 

The researchers discovered that the fluctuations of the nuclear membrane were systematic and predictable. The wobbles in nuclear membrane shape varied in amplitude, which gradually decreased over the course of the cell-division cycle. Thus, the degree to which a cell’s nuclear membrane is flickering “can serve as an internal clock of the cell, telling you at what stage in the cell cycle the cell is,” said senior author Zidovska.

These new findings of rapid nuclear fluctuations in living cells suggest opportunities for increased insights into the workings of healthy cells, and may also provide opportunities for better understanding of abnormal cells. For example, “developmental and inherited disorders such as cardiomyopathy, muscular dystrophy, and cancer” are already known to involve structural and functional errors in the nuclear membrane. 

The researchers are hopeful that scientific applications for this newly revealed internal clock inside our cells…are only a matter of time. (Proceedings of the National Academy of Sciences)