Contributed Talk

Velocity waves in rotating multicellular spheroids

Tom Brandstätter¹, David Brückner¹, Yu Long Han², Ricard Alert^3,4, Ming Guo², Chase P. Broedersz⁵

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A defining feature of many cellular tissues including developing tumors is collective cell migration in three-dimensional and often curved environments. A common and conceptually simple case is a spherically confined cell tissue. Such a geometry naturally appears during many cellular processes including tumor progression, as well as in in vitro model systems known as multicellular spheroids. Remarkably, in their spherical confinement, these cell clusters frequently exhibit collective rotational motion. However, it remains unclear how collective migration in such spheroids emerges from the interplay of active cell motility, cell-cell interactions, and the response to spatial cues like the closed topology and the positive curvature of the spherical geometry. We study cell trajectories in collectively rotating mammary spheroids - a model system for breast cancer progression. Strikingly, we discover that the cells migrating in spheroids exhibit a velocity wave propagating along the equator with a wavelength equal to the spheroid perimeter. Moreover, we find that the equatorial wave is part of an intricate global flow pattern of coordinated cell motion across the spheroid surface that involves cell motion over the spheroid poles as well as topological defects. Using a minimal active particle model, we reveal that this mode of migration has its origin in active flocking behavior of a confluent cell layer constrained on a positively curved surface. Therefore, we show that the velocity wave is a generic mode of collective cell migration, which could manifest in a wide variety of three-dimensional tissues with curved geometries like embryos and tumors.