title: The role of fluctuations and stress on the effective viscosity of cell aggregates.
abstract: Cell aggregates are a tool for in vitro studies of morphogenesis, cancer invasion, and tissue engineering. They respond to mechanical forces as a complex rather than simple liquid. To change an aggregate's shape, cells have to overcome energy barriers. If cell shape fluctuations are active enough, the aggregate spontaneously relaxes stresses ("fluctuation-induced flow"). If not, changing the aggregate's shape requires a sufficiently large applied stress ("stress-induced flow"). To capture this distinction, we develop a mechanical model of aggregates based on their cellular structure. At stress lower than a characteristic stress tau*, the aggregate as a whole flows with an apparent viscosity eta*, and at higher stress it is a shear-thinning fluid. An increasing cell-cell tension results in a higher eta* (and thus a slower stress relaxation time t(c)). Our constitutive equation fits experiments of aggregate shape relaxation after compression or decompression in which irreversibility can be measured; we find t(c) of the order of 5 h for F9 cell lines. Predictions also match numerical simulations of cell geometry and fluctuations. We discuss the deviations from liquid behavior, the possible overestimation of surface tension in parallel-plate compression measurements, and the role of measurement duration.
authors.affiliation: Laboratoire de Spectrométrie Physique, Unité Mixte de Recherche 5588, Université Grenoble I and Centre National de la Recherche Scientifique, 140 Avenue de la Physique, F-38402 Martin d'Hères Cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marmottant
authors.forename: Abbas
authors.initials: A
authors.lastname: Mgharbel
authors.forename: Jos
authors.initials: J
authors.lastname: Käfer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Audren
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Rieu
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Vial
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van der Sanden
authors.forename: Athanasius F M
authors.initials: AF
authors.lastname: Marée
authors.forename: François
authors.initials: F
authors.lastname: Graner
authors.forename: Hélène
authors.initials: H
authors.lastname: Delanoë-Ayari
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D002449:Cell Aggregation / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor / Q000166:cytology / Q000502:physiology; D048429:Cell Size; D002477:Cells / Q000166:cytology*; D019245:Compressive Strength; D004548:Elasticity; D004655:Emulsions; D051379:Mice; D013314:Stress, Mechanical; D014783:Viscosity
chemical_list: D004655:Emulsions