How cells flow in the spreading of cellular aggregates.
Like liquid droplets, cellular aggregates, also called "living droplets," spread onto adhesive surfaces. When deposited onto fibronectin-coated glass or polyacrylamide gels, they adhere and spread by protruding a cellular monolayer (precursor film) that expands around the droplet. The dynamics of spreading results from a balance between the pulling forces exerted by the highly motile cells at the periphery of the film, and friction forces associated with two types of cellular flows: (i) permeation, corresponding to the entry of the cells from the aggregates into the film; and (ii) slippage as the film expands. We characterize these flow fields within a spreading aggregate by using fluorescent tracking of individual cells and particle imaging velocimetry of cell populations. We find that permeation is limited to a narrow ring of width ξ (approximately a few cells) at the edge of the aggregate and regulates the dynamics of spreading. Furthermore, we find that the subsequent spreading of the monolayer depends heavily on the substrate rigidity. On rigid substrates, the migration of the cells in the monolayer is similar to the flow of a viscous liquid. By contrast, as the substrate gets softer, the film under tension becomes unstable with nucleation and growth of holes, flows are irregular, and cohesion decreases. Our results demonstrate that the mechanical properties of the environment influence the balance of forces that modulate collective cell migration, and therefore have important implications for the spreading behavior of tissues in both early development and cancer.
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 168, Institut Curie, 75248 Paris Cedex 05, France;
Grégory
G
Beaune
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 168, Institut Curie, 75248 Paris Cedex 05, France;
Tomita Vasilica
TV
Stirbat
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 168, Institut Curie, 75248 Paris Cedex 05, France;
Nada
N
Khalifat
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 168, Institut Curie, 75248 Paris Cedex 05, France;
Olivier
O
Cochet-Escartin
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 168, Institut Curie, 75248 Paris Cedex 05, France;
Simon
S
Garcia
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Institut Curie, 75248 Paris Cedex 05, France;
Vasily Valérïévitch
VV
Gurchenkov
Departments of Biomedical Engineering and Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI 53706; and.
Michael P
MP
Murrell
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 144, Institut Curie, 75248 Paris Cedex 05, France.
Sylvie
S
Dufour
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 168, Institut Curie, 75248 Paris Cedex 05, France;
Damien
D
Cuvelier
University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 168, Institut Curie, 75248 Paris Cedex 05, France; francoise.brochard@curie.fr.
Françoise
F
Brochard-Wyart
D000180:Acrylic Resins; D000269:Adhesives; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018450:Disease Progression; D017276:Friction; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives; D008164:Luminescent Proteins / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology*; D014906:Wetting Agents; D000097573:Red Fluorescent Protein
D000180:Acrylic Resins; D000269:Adhesives; D015820:Cadherins; D049452:Green Fluorescent Proteins; D008050:Lipid A; D008164:Luminescent Proteins; D014906:Wetting Agents; D000097573:Red Fluorescent Protein; C016680:polyacrylamide gels; C048988:GLA 27
tissue dynamics; tissue mechanosensitivity; wetting