12th Annual Symposium
Physics of Cancer
Leipzig, Germany
Aug 30 - Sept 1, 2021
Contributed Talk
Velocity waves in rotating multicellular spheroids
Tom Brandstätter1, David Brückner1, Yu Long Han2, Ricard Alert3,4, Ming Guo2, Chase P. Broedersz5
1Arnold-Sommerfeld-Center for Theoretical Physics, Ludwig-Maximilians- Universität München, Theresienstrasse 37, 80333 Munich, Germany
2Department of Mechanical Engineering, Massachusetts Institute of Technology, 33 Massachusetts Ave, Cambridge, MA 02139, United States
3Lewis-Sigler Institute for Integrative Genomics, Princeton University, South Drive, Princeton University, Princeton, NJ 08544, United States
4Princeton Center for Theoretical Science, Princeton University, NJ, USA
5Department of Physics and Astronomy, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
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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.
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