Cellular-level left-right asymmetry, cell chirality, induces the chiral collective rotation of multicellular colony

The left-right (LR) asymmetric morphology of organs is essential for the development and maintenance of their functions in various species. In recent years, it has become clear that the LR asymmetry of organs originates from cell chirality, the LR asymmetric nature at the cellular level [1]. However, it is unclear how the cell chirality generates the LR asymmetry at the multicellular level. Here we show a mechanism of LR asymmetry formation at the multicellular level based on cell chirality. We previously found that Caco-2 cells, a typical cultured epithelial cell line derived from human colon cancer, exhibit stereotypical and directional cell chirality; when Caco-2 cells are cultured as single cells, their nuclei and cytoplasm rotate in the clockwise direction at a rate of 50°/h [2]. Interestingly, when Caco-2 forms multicellular colonies, the colonies also undergo a collective clockwise rotation at 10º/h. We revealed that the actomyosin cytoskeleton is essential for the formation of the collective rotation [2]. We also found that Caco-2 cells formed lamellipodia and focal adhesions LR asymmetrically during the collective colony rotation, which may be responsible for the chiral collective motion. Interestingly, the disruption of microtubules reversed the direction of collective rotation. The LR asymmetric formation of lamellipodia and focal adhesions was also reversed by inhibition of microtubule polymerization. We will discuss the possible mechanism and the mathematical model where cell chirality induces multicellular chiral rotation depending on microtubules.