Topological defects are familiar characters in the physics of liquid crystals and active matter. They are points or lines where the local orientation field of a material cannot be defined smoothly, forcing the system into characteristic patterns such as vortices, spirals and asters. Over the past decade, dense sheets of cells have been shown to behave like active nematic liquid crystals, with elongated cells playing the role of rod-like molecules that constantly burn chemical energy to move and exert forces. Earlier work had revealed that defects in such monolayers can act as mechanical organizing centres: they concentrate stresses, attract cell death and extrusion in epithelia, and even mark the sites where the freshwater polyp Hydra sprouts new tentacles. What remained unclear was how a defect could coordinate cell motion on large scales and drive the assembly of genuinely three-dimensional tissue.

The French team solved this problem by taking control of the defect itself. Instead of waiting for vortices to appear spontaneously in a disordered monolayer, they fabricated polydimethylsiloxane substrates engraved with concentric micro-rails. Myoblasts migrating on these tracks follow contact guidance, the tendency of elongated cells to align with underlying grooves, and so the pattern imposes a well-defined vortex of cell orientation with an integer topological charge of +1 at its centre. This experimental trick transformed a fleeting, hard-to-predict feature of active matter into a stationary, reproducible target that could be imaged for days with phase-contrast and confocal microscopy, and quantified with particle image velocimetry and custom orientation analysis.

The first surprise came before any three-dimensional structure appeared. For roughly the first twelve hours after the monolayer reached confluence, the cells did not simply circle the centre along the rails. Their velocity field underwent a dramatic reorganization: the azimuthal, ring-following motion gave way to a radial flow converging on the defect core, with cells migrating perpendicular to their long axis, along their short axis, toward the centre of the pattern. The researchers tracked this transition with an order parameter that distinguishes azimuthal from radial flow, and found that the convergent regime emerged across millimetre scales, a huge distance compared with the size of a single cell. A swirl in orientation, in other words, was broadcasting a coordinated traffic instruction to thousands of cells simultaneously.

That convergent traffic had immediate architectural consequences. Cells arriving at the core began to extrude out of the plane of the monolayer, climbing over their neighbours and forming a second layer roughly six micrometres thick. Crucially, this new layer was not a random heap. Confocal sections revealed that the second layer inherited the vortex orientation of the layer beneath it, and when a third layer appeared a day later, it too was vortex-aligned. The team found that the cells deposit their own extracellular matrix, including collagen IV, in patterns that mirror the orientation of the cells that laid it down. This secreted scaffold then guides the orientation of subsequent arrivals through contact guidance, creating a feedback loop in which each layer templates the one above it. The mound, in effect, was printing itself layer by layer, with the topological defect supplying the pattern.

As the structure matured over tens of hours, its internal architecture became even more sophisticated. Confocal reconstructions of fixed mounds showed that the nematic order varied systematically with altitude. Near the base, close to the core, cells adopted an aster-like arrangement pointing radially outward, while farther from the centre they retained the vortex configuration. At the apex of the mound, the orientation twisted into a spiral. Remarkably, despite these changes in appearance, the in-plane topological charge remained invariant and equal to +1 along the entire vertical axis of the mound, from the first layer to the summit. When the researchers compared mounds from different experiments and different ages, the profiles of their orientation order parameter collapsed onto a single master curve once rescaled by the maximum height, indicating that the mound possesses a self-similar, reproducible internal blueprint.

The growth mechanism itself proved equally elegant. By tracking fluorescently labelled cells shuttling between layers, the team documented a process they describe as interlayer permeation: cells do not simply stack passively at the core but percolate through the existing structure, moving between adjacent layers like fluid seeping through a porous medium. The flux between layers peaked at a specific radius, the boundary between the inner aster-like region and the outer vortex region, where the orientation order parameter crosses zero. Even more striking was a reversal of flow direction as the mound aged. Around thirty hours after confluence, cells near the axis of the mound, which had initially migrated inward, began to migrate outward, and this switch from convergent to divergent flow was mirrored by a local change in orientation from vortex to aster. The growing structure was not static; it continuously reorganized its own traffic patterns as it expanded.

To make sense of these observations, Carles Blanch-Mercader and Jacques Prost developed a theoretical model treating the mound as a stack of active nematic fluid layers. The framework incorporates the active anisotropic stresses generated by the cells, the stresses in the external single layer, and an interfacial stress between layers, and it reproduces the measured radial velocity profiles and permeation fluxes with remarkable fidelity. The radial velocity in the monolayer follows a one-over-radius power law characteristic of a converging flow, while the flux from the mound to the external medium decays exponentially. In the late stages, the bell-shaped profile of the mound can be modelled entirely by dynamics driven by the converging flows, without invoking cell proliferation as the dominant driver. Drug perturbations confirmed this hierarchy: when proliferation was blocked with mitomycin C, the mounds retained their wild-type organization, but when contractility was inhibited with blebbistatin or the ROCK inhibitor Y-27632, the ordered alignment was almost completely destroyed. The architecture, it turns out, is a mechanical phenomenon built on cellular forces, not a by-product of cell division.

The implications reach well beyond the culture dish. Cellular whorls and swirls have long been noted by pathologists as diagnostic features in brain tumours, ovarian cancer surfaces and fine-needle aspirates of papillary thyroid carcinoma, and defects in the mesothelium have been shown to suppress the clearance of ovarian cancer cells. The new results suggest a physical mechanism by which such swirling patterns could actively organize cells into multilayered, tumour-like masses, with convergent defect-driven flows feeding cells into the core and permeation spreading them through the structure. The same physics may operate in normal morphogenesis, where embryonic tissues fold, bud and layer themselves with exquisite precision, and recent work on lumen nucleation in embryos has already implicated topological defect transitions controlled by boundary geometry. By demonstrating that an integer topological defect alone, imposed by nothing more than a patterned surface, can orchestrate millimetre-scale flows and the assembly of a highly ordered three-dimensional tissue from a featureless monolayer, the study provides both a conceptual framework and an experimental platform. It suggests that the grammar of tissue construction may be written partly in the language of topology, and that learning to read and perhaps rewrite that grammar could one day inform strategies in regenerative medicine, tissue engineering and cancer therapy.

Subject of Research: Topological-defect-driven morphogenesis of three-dimensional cell mounds in active nematic monolayers

Article Title: Morphogenesis of a stratified cell mound at a vortex defect

Article References: Morphogenesis of a stratified cell mound at a vortex defect. (n.d.). https://doi.org/10.1038/s41567-026-03427-9

Image Credits: AI Generated

DOI: 10.1038/s41567-026-03427-9

Keywords: topological defects, active nematics, cell monolayers, morphogenesis, collective cell migration, myoblasts, interlayer permeation, biological physics, tissue engineering, tumorigenesis, contact guidance, Institut Curie

The study, published in Scientific Reports, was led by Professor Tamiki Komatsuzaki of Hokkaido University and focused on one of biology’s classic model organisms: the soil-dwelling amoeba Dictyostelium discoideum. This single-celled organism has long fascinated scientists because of what it does when food runs out. When bacteria are scarce and starvation sets in, the amoebas begin releasing a chemical signal called cyclic AMP, or cAMP. Neighboring cells detect the signal, respond by releasing more of it, and begin crawling toward its source. The result is a spreading chemical wave that sweeps across the colony, and the cells ride that wave toward one another, eventually assembling into a multicellular organism. This dramatic transformation helps the amoebas survive hostile conditions, and it recapitulates, in miniature, the kind of collective cell behavior that underlies development, immunity, and disease in animals.

For decades, researchers studying this aggregation process have faced a practical dilemma. One approach is to track individual cells, following each amoeba’s path frame by frame to see how it moves. That works reasonably well when cells are sparse, but it becomes nearly impossible once the cells crowd together during aggregation, when one cell’s trail blurs into its neighbor’s. A second approach is to measure the cAMP wave itself, determining the direction in which the chemical signal is traveling across the colony. But these two measurements have traditionally been carried out separately, leaving a crucial gap: no direct, simultaneous view of how the wave’s dynamics relate to what each individual cell is actually doing at that instant. “How individual cells read passing waves of chemical signals and translate them into coordinated group migration has been hard to pin down,” Komatsuzaki explained.

The new study closes that gap with an ingenious imaging strategy. The team used fluorescent microscopy to record both cell movement and cAMP levels at the same time, frame by frame, throughout the aggregation process. Then came the clever part. The researchers took their sharp images and deliberately blurred them by different amounts, creating a series of versions of the same footage at different spatial scales. To each blurred version, they applied a computational technique called particle image velocimetry, or PIV, a method originally developed in fluid dynamics to trace the flow of liquids and gases by tracking patterns of motion between successive frames.

The logic behind the multiscale blurring is elegant. In the sharpest images, the analysis picks out the trajectories of individual cells, revealing each amoeba’s personal path across the colony floor. But as the images are blurred more heavily, the small, jittery movements of individual cells average out, and what remains is the larger, smoother pattern of motion embedded in the colony as a whole — the signature of the cAMP wave itself. By analyzing the same footage at multiple scales simultaneously, the researchers could directly compare the dynamics of the chemical wave with the movements of individual cells throughout the entire experiment, without ever having to separate the cells physically or measure the wave by an independent method. The team describes the result as a multiscale Eulerian velocity vector field: a map of motion that captures both the fine-grained behavior of single cells and the coarse-grained behavior of the collective at every moment.

Armed with this technique, the researchers tracked the amoebas continuously from two to seventeen hours after the onset of starvation, covering the full arc of the aggregation process. What they saw was a strikingly consistent pattern of behavior. As a cAMP wave approaches a cell, the amoeba surges forward to meet it almost head-on, racing toward the incoming chemical signal. But when the wave crests and begins to recede, something unexpected happens: the cell does not reverse direction to chase the departing wave. Instead, its motion stays locked in the same direction it was already traveling, carrying it forward even as the signal moves away. Only after the wave has passed does the cell settle down, resting directionless in the trough of the wave until the next one arrives — at which point the entire cycle repeats.

Komatsuzaki offered a vivid analogy for this behavior. “It’s like watching a crowd of surfers paddle hard to catch a wave, ride it together, and then bob around waiting for the next one,” he said. The image is apt in more than spirit. Each amoeba behaves like a surfer who paddles furiously toward an incoming swell, gains momentum as the wave lifts, coasts in the same direction even after the wave has passed beneath, and then drifts idly until the next swell appears. No individual surfer needs to know where the shore is or what the other surfers are doing; the collective pattern emerges from each cell responding to the same passing wave at the same time.

The directional locking that the researchers observed is particularly significant for understanding the physics of chemotaxis, the process by which cells move toward chemical attractants. A naive expectation might be that a cell responding to a chemical gradient would simply follow the gradient, reversing course whenever the gradient reverses. The amoebas do something subtly different: their response to the wave is temporally asymmetric, with a strong forward surge during the rising phase of the wave and a persistence of motion during the falling phase. This asymmetry, repeated wave after wave across thousands of cells, is what allows the colony to funnel itself steadily inward toward the aggregation center. The large-scale cAMP waves, visualized in the team’s images as smooth ripples spreading across the colony, were found to move in a direction precisely opposite to the average direction of individual cell movement — a 180-degree reversal that becomes visible only when single-cell motion and wave motion are compared side by side.

According to the authors, the findings offer the first systematic map of how the amoebas’ collective behavior emerges from individual action. That map matters beyond the world of social amoebae. Because the imaging technique separates single-cell motion from collective motion in the same dataset, the team believes it could be applied to far more complex systems, including populations of mammalian cells. One tantalizing possibility is identifying which cells act as “leaders” — initiating and shaping the waves — and which act as “followers,” responding to signals generated by others. In immune responses, where swarming neutrophils and other cells coordinate their pursuit of pathogens, and in cancer biology, where collectively invading tumor cells move through tissue in coordinated groups, such leader-follower dynamics are thought to play a decisive role but are notoriously hard to disentangle.

The study also demonstrates the value of borrowing tools from other disciplines. Particle image velocimetry was developed to measure fluid flow in wind tunnels and rivers, not to watch amoebas crawl across a petri dish. By adapting it to multiscale biological imaging, the researchers have created a method that treats a cell colony like a flowing medium with structure at every scale — a perspective that may prove broadly useful for studying active matter, tissue mechanics, and developmental biology. For now, the work provides something biologists have long lacked: a direct, quantitative picture of the moment when solitary cells stop being solitary. In the starved amoeba’s simple act of paddling toward a chemical wave and riding it together with its neighbors lies a principle that echoes through wound healing, immune defense, and cancer spread — the principle that a crowd, given the right signal, can behave like a single living thing.

Subject of Research: Collective cell migration in Dictyostelium discoideum via cAMP chemotactic wave signaling

Article Title: Study reveals how individual cells ‘surf’ chemical waves to form a collective

Article References: Study reveals how individual cells ‘surf’ chemical waves to form a collective. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Dictyostelium discoideum, cAMP, chemotaxis, collective cell migration, particle image velocimetry, fluorescent imaging, Hokkaido University, multicellularity, cell signaling, immune response, cancer biology, Scientific Reports