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Spindle-shaped cells orient together in vivo

Packed elongated fibroblasts cells tend to align along a common direction: they can be described as active nematics. When confined in a circular domain, these cells align with the domain boundary and display two characteristic defects along a diameter at well-defined locations. This behavior results from a low activity and high friction with the substrate.

In a letter published in Nature Physics, the groups of P. Silberzan (Biology-Inspired Physics at Mesoscales) and J.-F. Joanny (Physical Approach of Biological Problems) (CNRS/UPMC/Institut Curie) use the physics of Liquid Crystals to understand the dynamics of this organization.

Most spindle-shaped cells such the ones constituting muscles, but also sarcomas, routinely self-organize by aligning together along a common direction. When plated on a plane surface, they define domains of common orientation whose size is large compared to a cell size. In the terminology of liquid crystals, such an organization is called a “nematic” organization. However, unlike conventional liquid crystals, cells are active entities and this supracellular organization is best described as an “active nematic”. Active non-cellular nematics are generally dominated by activity, yielding complex chaotic movements and flows. However, the regime in which live spindle-shaped cells operate remained largely unexplored.

The domains in which cells are perfectly oriented are prevented from fusing together only by the presence of defects of orientation that are intrinsic to such structures. As with liquid crystals, these defects of orientation may be used to probe the behavior of the active nematic cellular systems. Monitoring closely the behavior of the defects in in vitro cultures shows that these active cellular nematics operate in a regime where activity is effectively damped by cell-substrate friction. When confined in infinite stripes, cells align with the physical boundaries and expel the defects, therefore they eventually define perfectly oriented domains over the width of the stripes that can reach half a millimeter. If the cells are now confined in mesoscopic microprinted circular domains, the system evolves toward a configuration where two identical disclinations face each other along a diameter. The positions of these defects measured over hundreds of patterns are independent on average of the size of the disk, the cells’ activity or even the cell type. These results show that, because of the high cell-surface friction, the cells behave as classical liquid crystals and, therefore, that these cell-based systems operate in a regime much more stable than other active nematics, which is likely to be required for their biological function.

Original Article in Nature Physics:
Topological defects in confined populations of spindle-shaped cells

Image © P. Silberzan/Institut Curie
Packed elongated fibroblasts cells tend to align along a common direction: they can be described as active nematics. When confined in a circular domain, these cells align with the domain boundary and display two characteristic defects along a diameter at well-defined locations. This behavior results from a low activity and high friction with the substrate.