Figure 1: Microscopy image showing the concentric pattern of F-actin, which gives rise to the clockwise rotation of the nucleus cytoplasm (the colors indicate the height of the F-actin). © 2025 RIKEN Center for Biosystems Dynamics Research
RIKEN researchers have discovered how right-handed molecules in our cells can give rise to cells that are not symmetrical about their central axes1. This discovery is a key step toward determining why most of our organs lack left-right symmetry.
It's conceivable that if some molecules that make up our cells were twisted in the opposite direction, our hearts would be on the right side of our bodies rather than on the left.
That's because the difference between the left and right sides of our organs may originate from the 'handedness', or chirality, of cells, which in turn comes from the chirality of molecules in cells.
However, the link between the chirality of molecules and cellular chirality is largely unknown. Many molecules in cells are chiral, including DNA and some amino acids and proteins, but it's not clear which ones convey their chirality to cells.
The team lead by Tatsuo Shibata of the RIKEN Center for Biosystems Dynamics Research first became interested in this question while studying genital discs in flies, which always rotate in a clockwise direction. They wanted to trace this phenomenon back to its molecule-level source.
"Through our work with flies, we became interested in working out how tissue-level chirality emerges from the chirality of individual cells, and how the chirality of individual cells emerges from the molecular-level chirality."
Now, by studying the chiral behaviors of individual cells, Shibata and co-workers have found that the cells' scaffolding, or cytoskeleton, gives rise to the cell's chirality.
When single cells were placed on a substrate, their nuclei and surrounding cytoplasm rotated in a clockwise direction when viewed from above. This rotational motion is driven by the concentric pattern of the actomyosin filaments that make up the cytoskeleton.
This finding implies that the cell nucleus can rotate even when there is no chiral orientation of the cytoskeleton on a cellular level.
To confirm whether this mechanism was driving the rotation, the team created a 3D theoretical model of a cell and evaluated the effect of the molecular chirality of actin and myosin on it. The results revealed that the molecular scale torque generated by individual components of the cytoskeleton can generate rotation, even when cell-level chiral structures were absent.
These results help fill in a critical link in the chain from molecules to organs and bodies, the researchers say.
"Our findings provide new insights into how molecular chirality gives rise to cellular chirality," says Shibata. "They thus represent an important step toward understanding left-right symmetry breaking in tissues and organs."
Takaki Yamamoto (not in photo), Tomoki Ishibashi (first on the left in front row), Tatsuo Shibata (center of front row) and other co-workers (not in photo) have discovered that chirality in epithelial cells emerges through the dynamic concentric pattern of the actomyosin cytoskeleton. © 2025 RIKEN
