RESUMEN
Epithelial monolayers are two-dimensional cell sheets which compartmentalize the body and organs of multicellular organisms. Their morphogenesis during development or pathology results from patterned endogenous and exogenous forces and their interplay with tissue mechanical properties. In particular, bending of epithelia is thought to result from active torques generated by the polarization of myosin motors along their apicobasal axis. However, the contribution of these out-of-plane forces to morphogenesis remains challenging to evaluate because of the lack of direct mechanical measurement. Here we use epithelial curling to characterize the out-of-plane mechanics of epithelial monolayers. We find that curls of high curvature form spontaneously at the free edge of epithelial monolayers devoid of substrate in vivo and in vitro. Curling originates from an enrichment of myosin in the basal domain that generates an active spontaneous curvature. By measuring the force necessary to flatten curls, we can then estimate the active torques and the bending modulus of the tissue. Finally, we show that the extent of curling is controlled by the interplay between in-plane and out-of-plane stresses in the monolayer. Such mechanical coupling emphasizes a possible role for in-plane stresses in shaping epithelia during morphogenesis.
Asunto(s)
Epitelio/fisiología , Animales , Fenómenos Biomecánicos , Adhesión Celular , Línea Celular , Perros , Elasticidad , Estrés MecánicoRESUMEN
The formation of self-organized patterns is key to the morphogenesis of multicellular organisms, although a comprehensive theory of biological pattern formation is still lacking. Here, we propose a minimal model combining tissue mechanics with morphogen turnover and transport to explore routes to patterning. Our active description couples morphogen reaction and diffusion, which impact cell differentiation and tissue mechanics, to a two-phase poroelastic rheology, where one tissue phase consists of a poroelastic cell network and the other one of a permeating extracellular fluid, which provides a feedback by actively transporting morphogens. While this model encompasses previous theories approximating tissues to inert monophasic media, such as Turing's reaction-diffusion model, it overcomes some of their key limitations permitting pattern formation via any two-species biochemical kinetics due to mechanically induced cross-diffusion flows. Moreover, we describe a qualitatively different advection-driven Keller-Segel instability which allows for the formation of patterns with a single morphogen and whose fundamental mode pattern robustly scales with tissue size. We discuss the potential relevance of these findings for tissue morphogenesis.
Asunto(s)
Tipificación del Cuerpo/fisiología , Morfogénesis/fisiología , Transporte de Proteínas/fisiología , Animales , Diferenciación Celular/fisiología , Difusión , Cinética , Modelos BiológicosRESUMEN
Throughout embryonic development and adult life, epithelia are subjected to compressive deformations. While these have been shown to trigger mechanosensitive responses such as cell extrusion and differentiation, which span tens of minutes, little is known about how epithelia adapt to compression over shorter timescales. Here, using suspended epithelia, we uncover the immediate response of epithelial tissues to the application of in-plane compressive strains (5-80%). We show that fast compression induces tissue buckling followed by actomyosin-dependent tissue flattening that erases the buckle within tens of seconds, in both mono- and multi-layered epithelia. Strikingly, we identify a well-defined limit to this response, so that stable folds form in the tissue when compressive strains exceed a 'buckling threshold' of ~35%. A combination of experiment and modelling shows that this behaviour is orchestrated by adaptation of the actomyosin cytoskeleton as it re-establishes tissue tension following compression. Thus, tissue pre-tension allows epithelia to both buffer against deformation and sets their ability to form and retain folds during morphogenesis.
Asunto(s)
Actomiosina/química , Epitelio/fisiología , Animales , Cadherinas/fisiología , Fuerza Compresiva , Citoesqueleto , Perros , Elasticidad , Células Epiteliales/citología , Epitelio/embriología , Proteínas Fluorescentes Verdes , Células de Riñón Canino Madin Darby , Microscopía Confocal , Modelos Biológicos , Morfogénesis , Estrés Mecánico , ViscosidadRESUMEN
There is increasing evidence that mammalian cells not only crawl on substrates but can also swim in fluids. To elucidate the mechanisms of the onset of motility of cells in suspension, a model which couples actin and myosin kinetics to fluid flow is proposed and solved for a spherical shape. The swimming speed is extracted in terms of key parameters. We analytically find super- and subcritical bifurcations from a nonmotile to a motile state and also spontaneous polarity oscillations that arise from a Hopf bifurcation. Relaxing the spherical assumption, the obtained shapes show appealing trends.
RESUMEN
An essential question of morphogenesis is how patterns arise without preexisting positional information, as inspired by Turing. In the past few years, cytoskeletal flows in the cell cortex have been identified as a key mechanism of molecular patterning at the subcellular level. Theoretical and in vitro studies have suggested that biological polymers such as actomyosin gels have the property to self-organize, but the applicability of this concept in an in vivo setting remains unclear. Here, we report that the regular spacing pattern of supracellular actin rings in the Drosophila tracheal tubule is governed by a self-organizing principle. We propose a simple biophysical model where pattern formation arises from the interplay of myosin contractility and actin turnover. We validate the hypotheses of the model using photobleaching experiments and report that the formation of actin rings is contractility dependent. Moreover, genetic and pharmacological perturbations of the physical properties of the actomyosin gel modify the spacing of the pattern, as the model predicted. In addition, our model posited a role of cortical friction in stabilizing the spacing pattern of actin rings. Consistently, genetic depletion of apical extracellular matrix caused strikingly dynamic movements of actin rings, mirroring our model prediction of a transition from steady to chaotic actin patterns at low cortical friction. Our results therefore demonstrate quantitatively that a hydrodynamical instability of the actin cortex can trigger regular pattern formation and drive morphogenesis in an in vivo setting.
Asunto(s)
Actinas/metabolismo , Células Epiteliales/metabolismo , Animales , Drosophila/embriología , Desarrollo Embrionario , Modelos BiológicosRESUMEN
The importance of collective cellular migration during embryogenesis and tissue repair asks for a sound understanding of underlying principles and mechanisms. Here, we address recent in vitro experiments on cell monolayers, which show that the advancement of the leading edge relies on cell proliferation and protrusive activity at the tissue margin. Within a simple viscoelastic mechanical model amenable to detailed analysis, we identify a key parameter responsible for tissue expansion, and we determine the dependence of the monolayer velocity as a function of measurable rheological parameters. Our results allow us to discuss the effects of pharmacological perturbations on the observed tissue dynamics.
Asunto(s)
Movimiento Celular , Proliferación Celular , Células/citología , Células/química , Modelos BiológicosRESUMEN
Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions. To perceive mechanical perturbations of different types and magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results of selective osmotic compressions of CT26 mouse cells within multicellular aggregates and global aggregate compressions, we show that global compressions have a strong impact on the aggregates growth and internal cell motility, while selective compressions of same magnitude have almost no effect. Both compressions alter the volume of individual cells in the same way over a shor-timescale, but, by draining the water out of the extracellular matrix, the global one imposes a residual compressive mechanical stress on the cells over a long-timescale, while the selective one does not. We conclude that the extracellular matrix is as a sensor that mechanically regulates cell proliferation and migration in a 3D environment.
Asunto(s)
Movimiento Celular , Proliferación Celular , Matriz Extracelular/fisiología , Morfogénesis/fisiología , Animales , Fenómenos Biomecánicos , Línea Celular , RatonesRESUMEN
Cell shape dynamics during development is tightly regulated and coordinated with cell fate determination. Triggered by an interplay between biochemical and mechanical signals, epithelia form complex tissues by undergoing coordinated cell shape changes, but how such spatiotemporal coordination is controlled remains an open question. To dissect biochemical signaling from purely mechanical cues, we developed a microfluidic system that experimentally triggers epithelial folding to recapitulate stereotypic deformations observed in vivo. Using this system, we observe that the apical or basal direction of folding results in strikingly different mechanical states at the fold boundary, where the balance between tissue tension and torque (arising from the imposed curvature) controls the spread of folding-induced calcium waves at a short timescale and induces spatial patterns of gene expression at longer timescales. Our work uncovers that folding-associated gradients of cell shape and their resulting mechanical stresses direct spatially distinct biochemical responses within the monolayer.
Asunto(s)
Forma de la Célula , Elasticidad , Células Epiteliales/química , Modelos Biológicos , Estrés Mecánico , Animales , Fenómenos Biomecánicos , Perros , Células de Riñón Canino Madin DarbyRESUMEN
This corrects the article DOI: 10.1103/PhysRevE.93.032410.
RESUMEN
Neurites, the long cellular protrusions that form the routes of the neuronal network, are capable of actively extending during early morphogenesis or regenerating after trauma. To perform this task, they rely on their cytoskeleton for mechanical support. In this paper, we present a three-component active gel model that describes neurites in the three robust mechanical states observed experimentally: collapsed, static, and motile. These states arise from an interplay between the physical forces driven by the growth of the microtubule-rich inner core of the neurite and the acto-myosin contractility of its surrounding cortical membrane. In particular, static states appear as a mechanical balance between traction and compression of these two parallel structures. The model predicts how the response of a neurite to a towing force depends on the force magnitude and recovers the response of neurites to several drug treatments that modulate the cytoskeleton active and passive properties.
Asunto(s)
Movimiento Celular , Fenómenos Mecánicos , Modelos Neurológicos , Neuritas/metabolismo , Fenómenos Biomecánicos , Adhesión Celular , Microtúbulos/metabolismoRESUMEN
Cellularised materials are composed of cells interfaced through specialised intercellular junctions that link the cytoskeleton of one cell to that of its neighbours allowing for transmission of forces. Cellularised materials are common in early development and adult tissues where they can be found in the form of cell sheets, cysts, or amorphous aggregates and in pathophysiological conditions such as cancerous tumours. Given the growing realisation that forces can regulate cell physiology and developmental processes, understanding how cellularised materials deform under mechanical stress or dissipate stress appear as key biological questions. In this review, we will discuss the dynamic mechanical properties of cellularised materials devoid of extracellular matrix.
Asunto(s)
Células/metabolismo , Animales , Fenómenos Biomecánicos , Agregación Celular , Humanos , Modelos Biológicos , Morfogénesis , ReologíaRESUMEN
The actomyosin cytoskeleton is a primary force-generating mechanism in morphogenesis, thus a robust spatial control of cytoskeletal positioning is essential. In this report, we demonstrate that actomyosin contractility and planar cell polarity (PCP) interact in post-mitotic Ciona notochord cells to self-assemble and reposition actomyosin rings, which play an essential role for cell elongation. Intriguingly, rings always form at the cells' anterior edge before migrating towards the center as contractility increases, reflecting a novel dynamical property of the cortex. Our drug and genetic manipulations uncover a tug-of-war between contractility, which localizes cortical flows toward the equator and PCP, which tries to reposition them. We develop a simple model of the physical forces underlying this tug-of-war, which quantitatively reproduces our results. We thus propose a quantitative framework for dissecting the relative contribution of contractility and PCP to the self-assembly and repositioning of cytoskeletal structures, which should be applicable to other morphogenetic events.
Asunto(s)
Actomiosina/metabolismo , Polaridad Celular , Ciona intestinalis/fisiología , Notocorda/fisiología , Transporte de Proteínas , Animales , Fenómenos Biofísicos , Forma de la Célula , Ciona intestinalis/citología , Ciona intestinalis/crecimiento & desarrollo , Contracción Muscular , Notocorda/citología , Notocorda/crecimiento & desarrollo , Multimerización de ProteínaRESUMEN
Eukaryotic cells possess motility mechanisms allowing them not only to self-propel but also to exert forces on obstacles (to push) and to carry cargoes (to pull). To study the inherent asymmetry between active pushing and pulling we model a crawling acto-myosin cell extract as a one-dimensional layer of active gel subjected to external forces. We show that pushing is controlled by protrusion and that the macroscopic signature of the protrusion dominated motility mechanism is concavity of the force-velocity relation. In contrast, pulling is driven by protrusion only at small values of the pulling force and it is replaced by contraction when the pulling force is sufficiently large. This leads to more complex convex-concave structure of the force-velocity relation; in particular, competition between protrusion and contraction can produce negative mobility in a biologically relevant range. The model illustrates active readjustment of the force generating machinery in response to changes in the dipole structure of external forces. The possibility of switching between complementary active mechanisms implies that if necessary "pushers" can replace "pullers" and vice versa.