Chiral Edge Current in Nematic Cell Monolayers

Abstract

Collectively migrating cells in living organisms are often guided by their local environment, including physical barriers and internal interfaces. Well-controlled in vitro experiments have shown that, when confined in adhesive stripes, monolayers of moderately active spindle-shaped cells self-organize at well-defined angle to the stripes’ longitudinal direction and spontaneously give rise to a simple shear flow, where the average cellular orientation smoothly varies across the system. However, the impact of physical boundaries on highly active, chaotic, multicellular systems is currently unknown, despite its potential relevance. In this work, we show that human fibrosarcoma cells (HT1080) close to an interface exhibit a spontaneous edge current with broken left-right symmetry, while in the bulk the cell flow remains chaotic. These localized edge currents result from an interplay between nematic order, microscopic chirality, and topological defects. Using a combination of in vitro experiments, numerical simulations, and theoretical work, we demonstrate the presence of a self-organized layer of+1/2defects anchored at the boundary and oriented at a well-defined angle close to, but smaller than, 90° with respect to the boundary direction. These self-organized defects act as local sources of chiral active stress generating the directed edge flows. Our work therefore highlights the impact of topology on the emergence of collective cell flows at boundaries. It also demonstrates the role of chirality in the emergence of edge flows. Since chirality and boundaries are common properties of multicellular systems, this work suggests a new possible mechanism for collective cellular flows.

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Plain Language Summary

Collective migration of cancer cells in the body is routinely observed close to confining structures such as muscle fibers or blood vessels. In vitro studies recreate such behavior by showing that fibrosarcoma cells collectively migrate at the border of their colony, even though within the monolayer, cell flows obey turbulent chaotic dynamics characterized by an irregular array of vortices generated by self-propelled units. Even more surprising is that the edge currents always flow in the same direction—somehow cells collectively distinguish between their left and right near the edge. To understand this situation, we look deeper at the organization of the cells within the monolayers.

Fibrosarcoma cells are elongated and align together, defining a patchwork of well-aligned domains between which orientational singularities (topological defects) position themselves. In the bulk of the monolayer, the position and orientation of these defects randomly change over time. However, close to the boundary, we find that comet-shaped “+1/2defects” orient themselves with an angle slightly smaller than 90° relative to the boundary, consistently tilting their tails to the right. Because of this left-right symmetry breaking, clockwise vortices are pushed closer to the border and generate the directed edge flow. Modeling the system as a chiral, active, nematic liquid crystal accounts well for our results and demonstrates that cell handedness is a critical ingredient for the emergence of the observed edge flows and not only for their direction.

We therefore suggest that acting on the cell handedness could interfere with collective migration of these cancer cells, which may offer new avenues in our understanding of the coupling between the handedness of single cells and collective behaviors.