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Tissue morphogenesis is driven by local cellular deformations that are powered by contractile actomyosin networks. How localized forces are transmitted across tissues to shape them at a mesoscopic scale is still unclear. Analyzing gastrulation in entire avian embryos, we show that it is driven by the graded contraction of a large-scale supracellular actomyosin ring at the margin between the embryonic and extraembryonic territories. The propagation of these forces is enabled by a fluid-like response of the epithelial embryonic disk, which depends on cell division. A simple model of fluid motion entrained by a tensile ring quantitatively captures the vortex-like “polonaise” movements that accompany the formation of the primitive streak. The geometry of the early embryo thus arises from the transmission of active forces generated along its boundary.

Neural crest cells migrate far and wide through a vertebrate embryo during development. Shellard et al. used Xenopus and zebrafish embryos to study how these clumps of mesenchymal cells migrate (see the Perspective by Adameyko). Movement was powered by a supracellular actomyosin cable that contracted around the rear of the clump. Similar supracellular contractility at the front was inhibited by a chemotactic signal. The imbalance in forces caused cells to rearrange so that the whole clump would be propelled forward. Science , this issue p. 339 ; see also p. 290 A rear engine drives collective chemotaxis in migrating Xenopus and zebrafish embryonic stem cells. Collective cell chemotaxis, the directed migration of cell groups along gradients of soluble chemical cues, underlies various developmental and pathological processes. We use neural crest cells, a migratory embryonic stem cell population whose behavior has been likened to malignant invasion, to study collective chemotaxis in vivo. Studying Xenopus and zebrafish, we have shown that the neural crest exhibits a tensile actomyosin ring at the edge of the migratory cell group that contracts in a supracellular fashion. This contractility is polarized during collective cell chemotaxis: It is inhibited at the front but persists at the rear of the cell cluster. The differential contractility drives directed collective cell migration ex vivo and in vivo through the intercalation of rear cells. Thus, in neural crest cells, collective chemotaxis works by rear-wheel drive.

Cells use actomyosin contractility to move through three-dimensional (3D) extracellular matrices. Contractility affects the type of protrusions cells use to migrate in 3D, but the mechanisms are unclear. In this work, we found that contractility generated high-pressure lobopodial protrusions in human cells migrating in a 3D matrix. In these cells, the nucleus physically divided the cytoplasm into forward and rear compartments. Actomyosin contractility with the nucleoskeleton-intermediate filament linker protein nesprin-3 pulled the nucleus forward and pressurized the front of the cell. Reducing expression of nesprin-3 decreased and equalized the intracellular pressure. Thus, the nucleus can act as a piston that physically compartmentalizes the cytoplasm and increases the hydrostatic pressure between the nucleus and the leading edge of the cell to drive lamellipodia-independent 3D cell migration.

Key Points The capability of cells to generate contractile forces originates from the activity of the molecular motor myosin II on its substrate actin filaments. Although the molecular constituents of contractility are well conserved across cell types, the organization of myosin and actin filaments varies widely from highly organized sarcomeres in striated muscle to non-sarcomeric organizations in smooth and non-muscle cells. In sarcomeres, actomyosin geometry regulates force transmission and is well understood. The non-sarcomeric organiazations of actomyosin require novel mechanisms of force transmission, from molecular to cellular length scales, and alternative mechanisms of contractility. Alternativee mechanisms of force transmission invoke nonlinear response of actin filaments and spatial localization of actin filament assembly. Non-sarcomeric actomyosin assemblies facilitate large shape changes, and mechanochemical feedback exists to coordinate assembly dynamics with contractility. Actomyosin networks are also used in cell mechanosensing and facilitate a novel mode of intracellular transport. Actomyosin-mediated contractility generates mechanical stress in animal cells and underlies muscle contraction, cell migration, cell division and tissue morphogenesis. Insight into the mechanics of actomyosin arrays that lack sarcomeric organization has revealed novel modes of force transmission and shown that diverse mechanical behaviours can arise from common molecular components. Actomyosin-mediated contractility is a highly conserved mechanism for generating mechanical stress in animal cells and underlies muscle contraction, cell migration, cell division and tissue morphogenesis. Whereas actomyosin-mediated contractility in striated muscle is well understood, the regulation of such contractility in non-muscle and smooth muscle cells is less certain. Our increased understanding of the mechanics of actomyosin arrays that lack sarcomeric organization has revealed novel modes of regulation and force transmission. This work also provides an example of how diverse mechanical behaviours at cellular scales can arise from common molecular components, underscoring the need for experiments and theories to bridge the molecular to cellular length scales.

We describe a multiscale model that incorporates force-dependent mechanical plasticity induced by interfiber cross-link breakage and stiffness-dependent cellular contractility to predict focal adhesion (FA) growth and mechanosensing in fibrous extracellular matrices (ECMs). The model predicts that FA size depends on both the stiffness of ECM and the density of ligands available to form adhesions. Although these two quantities are independent in commonly used hydrogels, contractile cells break cross-links in soft fibrous matrices leading to recruitment of fibers, which increases the ligand density in the vicinity of cells. Consequently, although the size of focal adhesions increases with ECM stiffness in nonfibrous and elastic hydrogels, plasticity of fibrous networks leads to a departure fromthe well-described positive correlation between stiffness and FA size. We predict a phase diagram that describes nonmonotonic behavior of FA in the space spanned by ECM stiffness and recruitment index, which describes the ability of cells to break cross-links and recruit fibers. The predicted decrease in FA size with increasing ECM stiffness is in excellent agreement with recent observations of cell spreading on electrospun fiber networks with tunable cross-link strengths and mechanics. Our model provides a framework to analyze cell mechanosensing in nonlinear and inelastic ECMs.

Contractile actomyosin rings drive various fundamental morphogenetic processes ranging from cytokinesis to wound healing. Actomyosin rings are generally thought to function by circumferential contraction. Here, we show that the spreading of the enveloping cell layer (EVL) over the yolk cell during zebrafish gastrulation is driven by a contractile actomyosin ring. In contrast to previous suggestions, we find that this ring functions not only by circumferential contraction but also by a flow-friction mechanism. This generates a pulling force through resistance against retrograde actomyosin flow. EVL spreading proceeds normally in situations where circumferential contraction is unproductive, indicating that the flow-friction mechanism is sufficient. Thus, actomyosin rings can function in epithelial morphogenesis through a combination of cable-constriction and flow-friction mechanisms.

Biological tissues acquire reproducible shapes during development through dynamic cell behaviors. Most of these behaviors involve the remodeling of cell–cell contacts. During epithelial morphogenesis, contractile actomyosin networks remodel cell–cell contacts by shrinking and extending junctions between lateral cell surfaces. However, actomyosin networks not only generate mechanical stresses but also respond to them, confounding our understanding of how mechanical stresses remodel cell–cell contacts. Here, we develop a two-point optical manipulation method to impose different stress patterns on cell–cell contacts in the early epithelium of the Drosophila embryo. The technique allows us to produce junction extension and shrinkage through different push and pull manipulations at the edges of junctions. We use these observations to expand classical vertex-based models of tissue mechanics, incorporating negative and positive mechanosensitive feedback depending on the type of remodeling. In particular, we show that Myosin-II activity responds to junction strain rate and facilitates full junction shrinkage. Altogether our work provides insight into how stress produces efficient deformation of cell–cell contacts in vivo and identifies unanticipated mechanosensitive features of their remodeling.

Cells select from a diverse repertoire of migration strategies. Recent developments in tunable biomaterials have helped identify how extracellular matrix properties influence migration, however, many settings lack the fibrous architecture characteristic of native tissues. To investigate migration in fibrous contexts, we independently varied the alignment and stiffness of synthetic 3D fiber matrices and identified two phenotypically distinct migration modes. In contrast to stiff matrices where cells migrated continuously in a traditional mesenchymal fashion, cells in deformable matrices stretched matrix fibers to store elastic energy; subsequent adhesion failure triggered sudden matrix recoil and rapid cell translocation. Across a variety of cell types, traction force measurements revealed a relationship between cell contractility and the matrix stiffness where this migration mode occurred optimally. Given the prevalence of fibrous tissues, an understanding of how matrix structure and mechanics influences migration could improve strategies to recruit repair cells to wound sites or inhibit cancer metastasis. How cells migrate in fibrous tissues is still poorly understood. Here, with synthetic 3D fibre matrices of controlled alignment and stiffness, the authors report that cells in stiff matrices move slowly and continuously, but in softer, deformable matrices cells can rapidly slingshot forward via stretch and recoil of matrix fibres.

Cellular mechanisms underlying the development of left–right asymmetry in tissues and embryos remain obscure. Here, the development of a chiral pattern of actomyosin was revealed by studying actin cytoskeleton self-organization in cells with isotropic circular shape. A radially symmetrical system of actin bundles consisting of α-actinin-enriched radial fibres (RFs) and myosin-IIA-enriched transverse fibres (TFs) evolved spontaneously into the chiral system as a result of the unidirectional tilting of all RFs, which was accompanied by a tangential shift in the retrograde movement of TFs. We showed that myosin-IIA-dependent contractile stresses within TFs drive their movement along RFs, which grow centripetally in a formin-dependent fashion. The handedness of the chiral pattern was shown to be regulated by α-actinin-1. Computational modelling demonstrated that the dynamics of the RF–TF system can explain the pattern transition from radial to chiral. Thus, actin cytoskeleton self-organization provides built-in machinery that potentially allows cells to develop left–right asymmetry. Bershadsky and colleagues show that cells confined to circular adhesive patterns exhibit defined and dynamic self-assembly of their actin cytoskeleton into a chiral pattern with defined handedness, potentially informing left–right cell asymmetry.

Damage to alveoli, the gas-exchanging region of the lungs, is a component of many chronic and acute lung diseases. In addition, insufficient generation of alveoli results in bronchopulmonary dysplasia, a disease of prematurity. Therefore visualising the process of alveolar development (alveologenesis) is critical for our understanding of lung homeostasis and for the development of treatments to repair and regenerate lung tissue. Here we show live alveologenesis, using long-term, time-lapse imaging of precision-cut lung slices. We reveal that during this process, epithelial cells are highly mobile and we identify specific cell behaviours that contribute to alveologenesis: cell clustering, hollowing and cell extension. Using the cytoskeleton inhibitors blebbistatin and cytochalasin D, we show that cell migration is a key driver of alveologenesis. This study reveals important novel information about lung biology and provides a new system in which to manipulate alveologenesis genetically and pharmacologically. The process of alveologenesis is incompletely understood, partly due to the lack of applicable real-time imaging methods. Here the authors describe the process of alveologenesis and the behaviour of epithelial cells in real-time, using widefield microscopy and image deconvolution in precision-cut lung slices, revealing the dominant role of epithelial cell migration.