Chiral edge currents in confined fibrosarcoma cells

TL;DR

This study reveals that confined fibrosarcoma cells exhibit chiral edge currents driven by topological defects and liquid crystalline order, leading to directed collective migration relevant for metastasis.

Contribution

It uncovers a novel mechanism of collective cell migration involving topological edge currents and chirality in confined cancer cell populations.

Findings

Confined fibrosarcoma cells form chiral edge currents.

Edge currents are driven by +1/2 topological defects.

Directed migration emerges from active hydrodynamics and topological defect interactions.

Abstract

During metastatic dissemination, streams of cells collectively migrate through a network of narrow channels within the extracellular matrix, before entering into the blood stream. This strategy is believed to outperform other migration modes, based on the observation that individual cancer cells can take advantage of confinement to switch to an adhesion-independent form of locomotion. Yet, the physical origin of this behaviour has remained elusive and the mechanisms behind the emergence of coherent flows in populations of invading cells under confinement are presently unknown. Here we demonstrate that human fibrosarcoma cells (HT1080) confined in narrow stripe-shaped regions undergo collective migration by virtue of a novel type of topological edge currents, resulting from the interplay between liquid crystalline (nematic) order, microscopic chirality and topological defects. Thanks to a combination of in vitro experiments and theory of active hydrodynamics, we show that, while heterogeneous and chaotic in the bulk of the channel, the spontaneous flow arising in confined populations of HT1080 cells is rectified along the edges, leading to long-ranged collective cell migration, with broken chiral symmetry. These edge currents are fuelled by layers of +1/2 topological defects, orthogonally anchored at the channel walls and acting as local sources of chiral active stress. Our work highlights the profound correlation between confinement and collective migration in multicellular systems and suggests a possible mechanism for the emergence of directed motion in metastatic cancer.