Yamamoto Takaki, Ishibashi Tomoki, Mimori-Kiyosue Yuko, Hiver Sylvain, Tokushige Naoko, Tarama Mitsusuke, Takeichi Masatoshi, Shibata Tatsuo
Laboratory for Physical Biology, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Nonequilibrium Physics of Living Matter RIKEN Hakubi Research Team, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Elife. 2025 Jul 8;14:e102296. doi: 10.7554/eLife.102296.
The chirality of tissues and organs is essential for their proper function and development. Tissue-level chirality derives from the chirality of individual cells that comprise the tissue, and cellular chirality is considered to emerge through the organization of chiral molecules within the cell. However, the principle of how molecular chirality leads to cellular chirality remains unresolved. To address this fundamental question, we experimentally studied the chiral behaviors of isolated epithelial cells derived from a carcinoma line and developed a theoretical understanding of how their behaviors arise from molecular-level chirality. We first found that the nucleus undergoes clockwise rotation, accompanied by robust cytoplasmic circulation in the same direction. During the rotation, actin and Myosin IIA assemble into the stress fibers with a vortex-like chiral orientation at the ventral side of the cell periphery, concurrently forming a concentric pattern at the dorsal side. Further analysis revealed that the intracellular rotation is driven by the concentric actomyosin filaments located dorsally, not by the ventral vortex-like chiral stress fibers. To elucidate how these concentric actomyosin filaments induce chiral rotation, we analyzed a theoretical model developed based on the theory of active chiral fluid. This model demonstrated that the observed cell-scale unidirectional rotation is driven by the molecular-scale chirality of actomyosin filaments even in the absence of cell-scale chiral orientational order. Our study thus provides novel mechanistic insights into how the molecular chirality is organized into the cellular chirality, representing an important step toward understanding left-right symmetry breaking in tissues and organs.
组织和器官的手性对于其正常功能和发育至关重要。组织水平的手性源自构成组织的单个细胞的手性，而细胞手性被认为是通过细胞内手性分子的组织而出现的。然而，分子手性如何导致细胞手性的原理仍未得到解决。为了解决这个基本问题，我们通过实验研究了源自癌细胞系的分离上皮细胞的手性行为，并对它们的行为如何从分子水平的手性产生形成了理论理解。我们首先发现细胞核进行顺时针旋转，同时伴随着相同方向的强烈细胞质循环。在旋转过程中，肌动蛋白和肌球蛋白IIA在细胞周边腹侧组装成具有涡旋状手性取向的应力纤维，同时在背侧形成同心图案。进一步分析表明，细胞内旋转是由位于背侧的同心肌动球蛋白丝驱动的，而不是由腹侧涡旋状手性应力纤维驱动的。为了阐明这些同心肌动球蛋白丝如何诱导手性旋转，我们分析了一个基于活性手性流体理论开发的理论模型。该模型表明，即使在没有细胞尺度手性取向顺序的情况下，观察到的细胞尺度单向旋转也是由肌动球蛋白丝的分子尺度手性驱动的。因此，我们的研究为分子手性如何组织成细胞手性提供了新的机制见解，代表了理解组织和器官左右对称性打破的重要一步。
