3D Hydrogel Encapsulation Regulates Nephrogenesis in Kidney Organoids.

Stem cell-derived kidney organoids contain nephron segments that recapitulate morphological and functional aspects of the human kidney. However, directed differentiation protocols for kidney organoids are largely conducted using biochemical signals to control differentiation. Here, the hypothesis that mechanical signals regulate nephrogenesis is investigated in 3D culture by encapsulating kidney organoids within viscoelastic alginate hydrogels with varying rates of stress relaxation. Tubular nephron segments are significantly more convoluted in kidney organoids differentiated in encapsulating hydrogels when compared with those in suspension culture. Hydrogel viscoelasticity regulates the spatial distribution of nephron segments within the differentiating kidney organoids. Consistent with these observations, a particle-based computational model predicts that the extent of deformation of the hydrogel-organoid interface regulates the morphology of nephron segments. Elevated extracellular calcium levels in the culture medium, which can be impacted by the hydrogels, decrease the glomerulus-to-tubule ratio of nephron segments. These findings reveal that hydrogel encapsulation regulates nephron patterning and morphology and suggest that the mechanical microenvironment is an important design variable for kidney regenerative medicine.

A mechanochemical model recapitulates distinct vertebrate gastrulation modes.

During vertebrate gastrulation, an embryo transforms from a layer of epithelial cells into a multilayered gastrula. This process requires the coordinated movements of hundreds to tens of thousands of cells, depending on the organism. In the chick embryo, patterns of actomyosin cables spanning several cells drive coordinated tissue flows. Here, we derive a minimal theoretical framework that couples actomyosin activity to global tissue flows. Our model predicts the onset and development of gastrulation flows in normal and experimentally perturbed chick embryos, mimicking different gastrulation modes as an active stress instability. Varying initial conditions and a parameter associated with active cell ingression, our model recapitulates distinct vertebrate gastrulation morphologies, consistent with recently published experiments in the chick embryo. Altogether, our results show how changes in the patterning of critical cell behaviors associated with different force-generating mechanisms contribute to distinct vertebrate gastrulation modes via a self-organizing mechanochemical process.

Learning to write with the fluid rope trick.

Direct ink writing, a versatile method of 3D and 4D printing, requires the precise placement of a nozzle just above the print surface to prevent fluid instabilities that cause deviations from the prescribed print path. But what if one could harness the instability associated with the spontaneously folding or coiling of a thin stream of viscous fluid, i.e. use the "fluid rope trick" to write specified patterns on a substrate? Here we use Deep Reinforcement Learning to derive control strategies for the motion of the extruding nozzle and thus the fluid patterns that are deposited on the surface. The method proceeds by having a learner (nozzle) repeatedly interact with the environment (a viscous filament simulator), and improves its strategy using the results of this experience. We demonstrate the outcome of the learned control instructions using experiments to manipulate a falling viscous jet and create cursive writing patterns and Pollockian paintings on substrates.

Contractility-Induced Phase Separation in Active Solids.

Experiments over many decades are suggestive that the combination of cellular contractility and active phase separation in cell-matrix composites can enable spatiotemporal patterning in multicellular tissues across scales. To characterize these phenomena, we provide a general theory that incorporates active cellular contractility into the classical Cahn-Hilliard-Larché model for phase separation in passive viscoelastic solids. Within this framework, we show how a homogeneous cell-matrix mixture can be destabilized by activity via either a pitchfork or Hopf bifurcation, resulting in stable phase separation and/or traveling waves. Numerical simulations of the full equations allow us to track the evolution of the resulting self-organized patterns in periodic and mechanically constrained domains, and in different geometries. Altogether, our study underscores the importance of integrating both cellular activity and mechanical phase separation in understanding patterning in soft, active biosolids in both in vivo and in vitro settings.

Beak morphometry and morphogenesis across avian radiations.

Adaptive avian radiations associated with the diversification of bird beaks into a multitude of forms enabling different functions are exemplified by Darwin's finches and Hawaiian honeycreepers. To elucidate the nature of these radiations, we quantified beak shape and skull shape using a variety of geometric measures that allowed us to collapse the variability of beak shape into a minimal set of geometric parameters. Furthermore, we find that just two measures of beak shape-the ratio of the width to length and the normalized sharpening rate (increase in the transverse beak curvature near the tip relative to that at the base of the beak)-are strongly correlated with diet. Finally, by considering how transverse sections to the beak centreline evolve with distance from the tip, we show that a simple geometry-driven growth law termed 'modified mean curvature flow' captures the beak shapes of Darwin's finches and Hawaiian honeycreepers. A surprising consequence of the simple growth law is that beak shapes that are not allowed based on the developmental programme of the beak are also not observed in nature, suggesting a link between evolutionary morphology and development in terms of growth-driven developmental constraints.

Evaporation-Driven Cellular Patterns in Confined Hyperelastic Hydrogels.

When a hyperelastic hydrogel confined between two parallel glass plates begins to dry from a lateral boundary, the volume lost by evaporation is accommodated by an inward displacement of the air-hydrogel interface that induces an elastic deformation of the hydrogel. Once a critical front displacement is reached, we observe intermittent fracture events initiated by a geometric instability resulting in localized bursts at the interface. These bursts relax the stresses and irreversibly form air cavities that lead to cellular networks. We show that the spatial extent of the strain field prior to a burst, influenced by the air-hydrogel interfacial tension and the confinement of the gel, determines the characteristic size of the cavities.

How to Grow a Flat Leaf.

Growing a flat lamina such as a leaf is almost impossible without some feedback to stabilize long wavelength modes that are easy to trigger since they are energetically cheap. Here we combine the physics of thin elastic plates with feedback control theory to explore how a leaf can remain flat while growing. We investigate both in-plane (metric) and out-of-plane (curvature) growth variation and account for both local and nonlocal feedback laws. We show that a linearized feedback theory that accounts for both spatially nonlocal and temporally delayed effects suffices to suppress long wavelength fluctuations effectively and explains recently observed statistical features of growth in tobacco leaves. Our work provides a framework for understanding the regulation of the shape of leaves and other leaflike laminar objects.

Statics and diffusive dynamics of surfaces driven by p-atic topological defects.

Inspired by epithelial morphogenesis, we consider a minimal model for the shaping of a surface driven by p-atic topological defects. We show that a positive (negative) defect can dynamically generate a (hyperbolic) cone whose shape evolves diffusively, and predict that a defect of charge + 1/p leads to a final semi-cone angle ß which satisfies the inequality . By exploiting the fact that for axisymmetric surfaces, the extrinsic geometry is tightly coupled to the intrinsic geometry, we further show that the resulting stationary shape of a membrane with negligible bending modulus and embedded polar order is a deformed lemon with two defects at antipodal points. Finally, we close by pointing out that our results may be relevant beyond epithelial morphogenesis in such contexts as shape transitions in macroscopic closed spheroidal surfaces such as pollen grains.

Ethics Inside the Black Box: Integrating Science and Technology Studies into Engineering and Public Policy Curricula.

There is growing need for hybrid curricula that integrate constructivist methods from Science and Technology Studies (STS) into both engineering and policy courses at the undergraduate and graduate levels. However, institutional and disciplinary barriers have made implementing such curricula difficult at many institutions. While several programs have recently been launched that mix technical training with consideration of "societal" or "ethical issues," these programs often lack a constructivist element, leaving newly-minted practitioners entering practical fields ill-equipped to unpack the politics of knowledge and technology or engage with skeptical publics. This paper presents a novel format for designing interdisciplinary coursework that combines conceptual content from STS with training in engineering and policy. Courses following this format would ideally be team taught by instructors with advanced training in diverse fields, and hence co-learning between instructors and disciplines is a key element of the format. Several instruments for facilitating both student and instructor collaborative learning are introduced. The format is also designed for versatility: in addition to being adaptable to both technical and policy training environments, topics are modularized around a conceptual core so that issues ranging from biotech to nuclear security can be incorporated to fit programmatic needs and resources.

Direct force measurement and loading on developing tissues in intact avian embryos.

Developmental morphogenesis is driven by tissue stresses acting on tissue rheology. Direct measurements of forces in small tissues (100 µm-1 mm) in situ, such as in early embryos, require high spatial precision and minimal invasiveness. Here, we introduce a control-based approach, tissue force microscopy (TiFM), that integrates a mechanical cantilever probe and live imaging with closed-loop feedback control of mechanical loading in early chicken embryos. By testing previously qualitatively characterized force-producing tissues in the elongating body axis, we show that TiFM quantitatively captures stress dynamics with high sensitivity. TiFM also provides the means to apply stable, minimally invasive and physiologically relevant loads to drive tissue deformation and to follow the resulting morphogenetic progression associated with large-scale cell movements. Together, TiFM allows us to control tissue force measurement and manipulation in small developing embryos, and promises to contribute to the quantitative understanding of complex multi-tissue mechanics during development.

Combined measures of mimetic fidelity explain imperfect mimicry in a brood parasite-host system.

The persistence of imperfect mimicry in nature presents a challenge to mimicry theory. Some hypotheses for the existence of imperfect mimicry make differing predictions depending on how mimetic fidelity is measured. Here, we measure mimetic fidelity in a brood parasite-host system using both trait-based and response-based measures of mimetic fidelity. Cuckoo finches Anomalospiza imberbis lay imperfectly mimetic eggs that lack the fine scribbling characteristic of eggs of the tawny-flanked prinia Prinia subflava, a common host species. A trait-based discriminant analysis based on Minkowski functionals-that use geometric and topological morphometric methods related to egg pattern shape and coverage-reflects this consistent difference between host and parasite eggs. These methods could be applied to quantify other phenotypes including stripes and waved patterns. Furthermore, by painting scribbles onto cuckoo finch eggs and testing their rate of rejection compared to control eggs (i.e. a response-based approach to quantify mimetic fidelity), we show that prinias do not discriminate between eggs based on the absence of scribbles. Overall, our results support relaxed selection on cuckoo finches to mimic scribbles, since prinias do not respond differently to eggs with and without scribbles, despite the existence of this consistent trait difference.

Matrix viscoelasticity controls spatiotemporal tissue organization.

Biomolecular and physical cues of the extracellular matrix environment regulate collective cell dynamics and tissue patterning. Nonetheless, how the viscoelastic properties of the matrix regulate collective cell spatial and temporal organization is not fully understood. Here we show that the passive viscoelastic properties of the matrix encapsulating a spheroidal tissue of breast epithelial cells guide tissue proliferation in space and in time. Matrix viscoelasticity prompts symmetry breaking of the spheroid, leading to the formation of invading finger-like protrusions, YAP nuclear translocation and epithelial-to-mesenchymal transition both in vitro and in vivo in a Arp2/3-complex-dependent manner. Computational modelling of these observations allows us to establish a phase diagram relating morphological stability with matrix viscoelasticity, tissue viscosity, cell motility and cell division rate, which is experimentally validated by biochemical assays and in vitro experiments with an intestinal organoid. Altogether, this work highlights the role of stress relaxation mechanisms in tissue growth dynamics, a fundamental process in morphogenesis and oncogenesis.

An additive framework for kirigami design.

We present an additive approach for the inverse design of kirigami-based mechanical metamaterials by focusing on the empty (negative) spaces instead of the solid tiles. By considering each negative space as a four-bar linkage, we identify a simple recursive relationship between adjacent linkages, yielding an efficient method for creating kirigami patterns. This allows us to solve the kirigami design problem using elementary linear algebra, with compatibility, reconfigurability and rigid-deployability encoded into an iterative procedure involving simple matrix multiplications. The resulting linear design strategy circumvents the solution of a non-convex global optimization problem and allows us to control the degrees of freedom in the deployment angle field, linkage offsets and boundary conditions. We demonstrate this by creating a large variety of rigid-deployable, compact, reconfigurable kirigami patterns. We then realize our kirigami designs physically using two simple but effective fabrication strategies with very different materials. Altogether, our additive approaches present routes for efficient mechanical metamaterial design and fabrication based on ori/kirigami art forms.

An allometric prior enhances acoustic niche partitioning signal.

The acoustic niche hypothesis suggests that vocal signals of sympatric animal species are structured so as to minimize acoustic interference and facilitate communication. Accordingly, each species attempts to establish its own acoustic bandwidth so that intra-species signals are not masked. Detecting a non-random partitioning of the frequency spectrum among sympatric species could constitute evidence for the existence of acoustic avoidance behaviour. However, results from previous studies have been mixed or inconclusive, possibly as a consequence of overlooking the importance of physiological and ecological constraints. Here we introduce an improved test that incorporates prior information on body mass to account for the allometric correlation between mass (size) and vocalization frequency. By correcting for the bias induced by this correlation, the new test uncovers evidence of acoustic niche partitioning as a function of frequency in several tropical bird communities that would not be detected under a more standard test. Separately, we introduce a spatial version of the acoustic partitioning test which, in theory, could prove effective when data are collected from multiple sites located in close spatial proximity.

A continuous statistical-geometric framework for normative and impaired gaits.

A quantitative analysis of human gait patterns in space-time provides an opportunity to observe variability within and across individuals of varying motor capabilities. Impaired gait significantly affects independence and quality of life, and thus a large part of clinical research is dedicated to improving gait through rehabilitative therapies. Evaluation of these paradigms relies on understanding the characteristic differences in the kinematics and underlying biomechanics of impaired and unimpaired locomotion, which has motivated quantitative measurement and analysis of the gait cycle. Previous analysis has largely been limited to a statistical comparison of manually selected pointwise metrics identified through expert knowledge. Here, we use a recent statistical-geometric framework, elastic functional data analysis (FDA), to decompose kinematic data into continuous 'amplitude' (spatial) and 'phase' (temporal) components, which can then be integrated with established dimensionality reduction techniques. We demonstrate the utility of elastic FDA through two unsupervised applications to post-stroke gait datasets. First, we distinguish between unimpaired, paretic and non-paretic gait presentations. Then, we use FDA to reveal robust, interpretable groups of differential response to exosuit assistance. The proposed methods aim to benefit clinical practice for post-stroke gait rehabilitation, and more broadly, to automate the quantitative analysis of motion.

Dynamics of cooperative excavation in ant and robot collectives.

The solution of complex problems by the collective action of simple agents in both biologically evolved and synthetically engineered systems involves cooperative action. Understanding the resulting emergent solutions requires integrating across the organismal behavior of many individuals. Here, we investigate an ecologically relevant collective task in black carpenter ants Camponotus pennsylvanicus: excavation of a soft, erodible confining corral. These ants show a transition from individual exploratory excavation at random locations to spatially localized collective exploitative excavation and escape from the corral. Agent-based simulations and a minimal continuum theory that coarse-grains over individual actions and considers their integrated influence on the environment leads to the emergence of an effective phase space of behaviors, characterized in terms of excavation strength and cooperation intensity. To test the theory over the range of both observed and predicted behaviors, we use custom-built robots (RAnts) that respond to stimuli to characterize the phase space of emergence (and failure) of cooperative excavation. Tuning the amount of cooperation between RAnts, allows us to vary the efficiency of excavation and synthetically generate the entire range of macroscopic phases predicted by our theory. Overall, our approach shows how the cooperative completion of tasks can arise from simple rules that involve the interaction of agents with a dynamically changing environment that serves as both an enabler and a modulator of behavior.

Active entanglement enables stochastic, topological grasping.

Grasping, in both biological and engineered mechanisms, can be highly sensitive to the gripper and object morphology, as well as perception and motion planning. Here, we circumvent the need for feedback or precise planning by using an array of fluidically actuated slender hollow elastomeric filaments to actively entangle with objects that vary in geometric and topological complexity. The resulting stochastic interactions enable a unique soft and conformable grasping strategy across a range of target objects that vary in size, weight, and shape. We experimentally evaluate the grasping performance of our strategy and use a computational framework for the collective mechanics of flexible filaments in contact with complex objects to explain our findings. Overall, our study highlights how active collective entanglement of a filament array via an uncontrolled, spatially distributed scheme provides options for soft, adaptable grasping.

Safeguarding human-wildlife cooperation.

Human-wildlife cooperation occurs when humans and free-living wild animals actively coordinate their behavior to achieve a mutually beneficial outcome. These interactions provide important benefits to both the human and wildlife communities involved, have wider impacts on the local ecosystem, and represent a unique intersection of human and animal cultures. The remaining active forms are human-honeyguide and human-dolphin cooperation, but these are at risk of joining several inactive forms (including human-wolf and human-orca cooperation). Human-wildlife cooperation faces a unique set of conservation challenges, as it requires multiple components-a motivated human and wildlife partner, a suitable environment, and compatible interspecies knowledge-which face threats from ecological and cultural changes. To safeguard human-wildlife cooperation, we recommend: (i) establishing ethically sound conservation strategies together with the participating human communities; (ii) conserving opportunities for human and wildlife participation; (iii) protecting suitable environments; (iv) facilitating cultural transmission of traditional knowledge; (v) accessibly archiving Indigenous and scientific knowledge; and (vi) conducting long-term empirical studies to better understand these interactions and identify threats. Tailored safeguarding plans are therefore necessary to protect these diverse and irreplaceable interactions. Broadly, our review highlights that efforts to conserve biological and cultural diversity should carefully consider interactions between human and animal cultures. Please see AfricanHoneyguides.com/abstract-translations for Kiswahili and Portuguese translations of the abstract.

Active Nematic Defects and Epithelial Morphogenesis.

Inspired by recent experiments that highlight the role of nematic defects in the morphogenesis of epithelial tissues, we develop a minimal framework to study the dynamics of an active curved surface driven by its nematic texture. Allowing the surface to evolve via relaxational dynamics leads to a theory linking nematic defect dynamics, cellular division rates, and Gaussian curvature. Regions of large positive (negative) curvature and positive (negative) growth are colocalized with the presence of positive (negative) defects. In an ex-vivo setting of cultured murine neural progenitor cells, we show that our framework is consistent with the observed cell accumulation at positive defects and depletion at negative defects. In an in-vivo setting, we show that the defect configuration consisting of a bound +1 defect state, which is stabilized by activity, surrounded by two -1/2 defects can create a stationary ring configuration of tentacles, consistent with observations of a basal marine invertebrate Hydra.

Muscular hydraulics drive larva-polyp morphogenesis.

Development is a highly dynamic process in which organisms often experience changes in both form and behavior, which are typically coupled to each other. However, little is known about how organismal-scale behaviors such as body contractility and motility impact morphogenesis. Here, we use the cnidarian Nematostella vectensis as a developmental model to uncover a mechanistic link between organismal size, shape, and behavior. Using quantitative live imaging in a large population of developing animals, combined with molecular and biophysical experiments, we demonstrate that the muscular-hydraulic machinery that controls body movement also drives larva-polyp morphogenesis. We show that organismal size largely depends on cavity inflation through fluid uptake, whereas body shape is constrained by the organization of the muscular system. The generation of ethograms identifies different trajectories of size and shape development in sessile and motile animals, which display distinct patterns of body contractions. With a simple theoretical model, we conceptualize how pressures generated by muscular hydraulics can act as a global mechanical regulator that coordinates tissue remodeling. Altogether, our findings illustrate how organismal contractility and motility behaviors can influence morphogenesis.