Cell division: how molecular motors team up for separating cells
Cells are placed vertically in micro-fabricated cavities; cytokinetic rings of yeasts (schematically at the top) and mammalian cells (schematically at the bottom) are visible (yellow and green rings respectively). These structures are characterized by distinct collective dynamic of molecular motors.
© IGBMC / Team Daniel Riveline
July 1, 2016
The team of Daniel Riveline at IGBMC (CNRS, INSERM, University of Strasbourg) and at the Institute of Science and Supramolecular Engineering (ISIS, CNRS, University of Strasbourg), in collaboration with the team of Karsten Kruse (Saarland University, Germany) has revealed the mechanisms leading to physical separations of yeast and mammalian cells. These results are published in the journal Nature Communications, July 1st 2016.
Mitosis, or cell division, is a fundamental process in the living world allowing cell proliferation. It involves the division of a mother cell into two daughter cells. The last step of division is called cytokinesis and is accompanied by the formation of a cytokinetic ring. The latter is leading the physical separation of cells. From yeast to humans, this ring is composed of thousands of molecular motors and filaments in interaction - myosins and actin filaments. The same proteins are also involved in muscle contraction. To date, the way these motors and filaments interact collectively during cytokinesis was unknown.
Constrictions mechanisms are different for rings in yeast and in mammalian cells
After years of research initiated at the Rockefeller University, continued at the ISIS and at the IGBMC, the team of Daniel Riveline developed a new cell culture method with micro-fabricated three-dimensional structures. Individual cells are placed vertically in “egg cups for cells” to orient and capture cytokinetic rings in a single plane of observation. Thanks to this approach, researchers were able to determine the spatiotemporal organizations of motors during constriction in unprecedented ways.
Specifically, myosin motors self-organize differently in yeast and in mammalian rings. In yeast, myosin motors form clusters which undergo rotation. This movement allows transport of the wall machinery. In mammalian cells, myosin motors self-organize into clusters as well within the cytokinetic ring. But they remain stationary in their framework during cytokinesis, thereby allowing constriction itself. These distinct dynamics of myosin aggregates were modeled and reproduced by theoretical approaches by the team of Karsten Kruse. The associated mechanisms were further probed and validated by experiments in the team of Daniel Riveline.
This research suggests new regulatory rules through self-organization per se of collections of molecular motors. Motor clusters allow transport or forces application, depending on the modes of interaction between motors and filaments. Such phenomena should be generic in living matter, and as a consequence, this study opens new research avenues in developmental biology for explaining changes in shapes during embryogenesis. In addition, these findings may help to find innovative ways to stop uncontrolled cell proliferations in cancer.