Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression

Colloquium: Mechanical formalisms for tissue dynamics

The understanding of morphogenesis in living organisms has been renewed by tremendous progressin experimental techniques that provide access to cell-scale, quantitative information both on theshapes of cells within tissues and on the genes being expressed. This information suggests that ourunderstanding of the respective contributions of gene expression and mechanics, and of their crucialentanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assistthe design and interpretation of experiments, point out the main ingredients and assumptions, andultimately lead to predictions. The newly accessible local information thus calls for a reflectionon how to select suitable classes of mechanical models. We review both mechanical ingredientssuggested by the current knowledge of tissue behaviour, and modelling methods that can helpgenerate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and tissue scale ("inter-cell") contributions. We recall the mathematical framework developpedfor continuum materials and explain how to transform a constitutive equation into a set of partialdifferential equations amenable to numerical resolution. We show that when plastic behaviour isrelevant, the dissipation function formalism appears appropriate to generate constitutive equations;its variational nature facilitates numerical implementation, and we discuss adaptations needed in thecase of large deformations. The present article gathers theoretical methods that can readily enhancethe significance of the data to be extracted from recent or future high throughput biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few corrections to the published version, all in Appendix D.2 devoted to large deformation

Morphology and growth of polarized tissues

We study and classify the time-dependent morphologies of polarized tissues subject to anisotropic but spatially homogeneous growth. Extending previous studies, we model the tissue as a fluid, and discuss the interplay of the active stresses generated by the anisotropic cell division and three types of passive mechanical forces: viscous stresses, friction with the environment and tension at the tissue boundary. The morphology dynamics is formulated as a free-boundary problem, and conformal mapping techniques are used to solve the evolution numerically. We combine analytical and numerical results to elucidate how the different passive forces compete with the active stresses to shape the tissue in different temporal regimes and derive the corresponding scaling laws. We show that in general the aspect ratio of elongated tissues is non-monotonic in time, eventually recovering isotropic shapes in the presence of friction forces, which are asymptotically dominant

Subharmonic oscillations of collective molecular motors

We study a generic two-state model for an assembly of molecular motors which is described by means of a pair of integro-partial differential equations and leads to oscillatory motion in the presence of an elastic coupling to its environment. We discuss a reduction of the system to a minimal set of three ordinary differential equations that successfully capture the complex nonlinear dynamics of the full system. In the limit of high mobility and large elastic modulus, we report on the emergence of subharmonics in the power spectrum of the oscillations. This provides a rationale for the unexplained observation of secondary peaks in a minimal actomyosin system in vitro (Plaçais P.-Y

Turbulent Dynamics of Epithelial Cell Cultures

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Effective viscosity and dynamics of spreading epithelia: a solvable model

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Chiral edge currents in nematic cell monolayers

7 pages, 4 figuresInternational audienceDuring 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

Spontaneous shear flow in confined cellular nematics

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