The mechanical ratchet: A new mechanism of cell division uncovered

Cell division is an essential process for all life on earth, yet the exact mechanisms by which cells divide during early embryonic development have remained elusive – particularly for egg-laying species. Scientists from the Brugués group at the Cluster of Excellence Physics of Life (PoL) at TUD Dresden University of Technology have revealed a novel mechanism that explains how early embryonic cells may divide without forming a complete contractile ring, traditionally seen as essential for this process. The findings, published in Nature, challenge the long-standing textbook view of cell division, revealing how parts of the cytoskeleton, and material properties of the cell interior (or cytoplasm) cooperate to drive division through a ‘ratchet’ mechanism.    

In most species, cells divide by forming a contractile ring from a structural protein known as actin at the cell equator. This ring contracts like a purse-string, pinching the cell’s contents to result in two new cells. Although the ‘purse-string’ model of cell division is observed in many organisms, this is not the case for species with very large embryonic cells such as sharks, platypus, birds and reptiles. In these cases, the actin ring cannot fully close due to the cell’s immense size and large yolk sac. How exactly cell division takes place in these organisms remained an open question in the field, until now. “With such a large yolk in the embryonic cell, there is a geometric constraint. How does a contractile band, with loose ends, remain stable and generate enough force to divide these huge cells?” asked Alison Kickuth, a recently graduated PhD student from the Brugués group at the Cluster of Excellence Physics of Life (PoL) and lead author of the study. Their experiments, published in a seminal new study in Nature, have found an answer to this question.

The scientists studied zebrafish embryos, which divide rapidly and share the characteristic of having large, yolk-filled cells during early development. By precisely cutting the actin band with a laser, Alison observed that the band continued to ingress despite being severed, suggesting that anchoring points were distributed along the band, rather than at the ends. In addition, it seemed that microtubules, another essential part of the cytoskeleton, appeared to bend and splay in response to the laser cuts, and had a critical role in stabilizing the band during contraction. To clarify the role of microtubules in this process, the authors disrupted them in two separate experiments: by chemically inducing depolymerization (effectively stopping new microtubules from forming), and by physically disrupting them using an obstacle, in the form of a microscopic oil droplet. Without microtubules, the actin band collapsed, proving that microtubules are essential for holding the band in place, and provided both mechanical support and signalling during its formation.

Changes in the cytoskeleton are known to happen in other species as cell cycles progress. Importantly, the cell cycle is separated into distinct phases of activity; a mitotic phase (M-phase) where the DNA is divided, and an interphase, where a typical cell grows and replicates its DNA. After DNA has been divided, large structures made of microtubules called asters grow to span the entire cytoplasm. These asters are essential during interphase for deciding where the actin band will form and start contracting, marking the future cleavage plane. Given that microtubules are known to stiffen the cytoplasm in various cellular contexts, the authors sought to explore if asters would contribute to stiffening to help anchor the actin band. To investigate, the authors employed magnetic beads and observed their displacement under magnetic forces. These experiments allowed the scientists to measure changes in cytoplasmic stiffness during cell cycle stages. They found that the cytoplasm becomes stiffer during interphase, acting as a scaffold to stabilize the actin band. In turn, it becomes more fluid during M-phase, allowing the band’s ingression between the two future cells. These dynamic changes in stiffening and fluidization play a key role in the division process.

Only one question remained: How did the band remain stable throughout M-phase despite the cytoplasm becoming more fluid-like? By imaging the ends of the actin band over time, the team observed that although the band is unstable during M-phase while contracting, it did not collapse fully. Instead, this retraction is “rescued” due to the fast cell cycles in these early stages. In the following interphase when the cytoplasm stiffens again due to the asters reappearing, the band becomes re-stabilized. Then, the actin band continued ingressing during the next fluid-phase. These cycles of instability during M-phase and stabilization during interphase repeated over several cell cycles until division was complete. This alternating pattern acts like a ‘mechanical ratchet’, driving cell division without needing a fully-formed contractile ring. In this case, division is possible through the alternating material properties of the cytoplasm, and takes place over multiple cell cycles instead of just one.

“The temporal ratchet mechanism fundamentally alters our view of how cytokinesis works”, emphasized Jan Brugués, corresponding author of the study. This finding provided an effective solution for early cell divisions in cells that were too large for conventional cell division, and have rapid cell cycles. “Zebrafish are a fascinating case, as cytoplasmic division in their embryonic cells is inherently unstable. To overcome this instability, their cells divide rapidly, allowing ingression of the band over several cell cycles by alternating between stability and fluidisation until division is complete” highlighted Alison regarding this finding. This discovery represents a novel paradigm for understanding cell division in large embryonic cells and may apply broadly across species with yolk-rich embryos. Additionally, this study highlights temporal control of material properties in the cytoplasm as an important contributor to cellular processes, a role that may be expanded in future studies. Understanding these mechanisms will open new perspectives for studying development in different species.

Original publication: Alison Kickuth, Urša Uršič, Michael F. Staddon, Jan Brugués. A mechanical ratchet drives unilateral cytokinesis. Nature (2026). DOI: https://doi.org/10.1038/s41586-025-09915-x

Funding: This study was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC-2068–390729961- Cluster of Excellence Physics of Life of TU Dresden. Researchers were also supported by Volkswagen ‘Life’ grant number 96827.


About the Cluster of Excellence Physics of Life
Physics of Life (PoL) is one of five Clusters of Excellence at TU Dresden. PoL’s aim is to identify the physical laws underlying the organization of life in molecules, cells, and tissues. Scientists from physics, biology, and computer science come together to investigate how active matter in cells and tissues organizes itself into given structures and gives rise to life. PoL is funded by the DFG within the framework of the Excellence Strategy. It is a cooperation between scientists of the TU Dresden and research institutions of the DRESDEN-concept network, such as the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), the Max Planck Institute for the Physics of Complex Systems (MPI-PKS), the Leibniz Institute of Polymer Research (IPF) and the Helmholtz-Zentrum Dresden-Rossendorf (HZDR). https://physics-of-life.tu-dresden.de/