Geometric phase predicts locomotion performance in undulating living systems across scales.

Self-propelling organisms locomote via generation of patterns of self-deformation. Despite the diversity of body plans, internal actuation schemes and environments in limbless vertebrates and invertebrates, such organisms often use similar traveling waves of axial body bending for movement. Delineating how self-deformation parameters lead to locomotor performance (e.g. speed, energy, turning capabilities) remains challenging. We show that a geometric framework, replacing laborious calculation with a diagrammatic scheme, is well-suited to discovery and comparison of effective patterns of wave dynamics in diverse living systems. We focus on a regime of undulatory locomotion, that of highly damped environments, which is applicable not only to small organisms in viscous fluids, but also larger animals in frictional fluids (sand) and on frictional ground. We find that the traveling wave dynamics used by mm-scale nematode worms and cm-scale desert dwelling snakes and lizards can be described by time series of weights associated with two principal modes. The approximately circular closed path trajectories of mode weights in a self-deformation space enclose near-maximal surface integral (geometric phase) for organisms spanning two decades in body length. We hypothesize that such trajectories are targets of control (which we refer to as "serpenoid templates"). Further, the geometric approach reveals how seemingly complex behaviors such as turning in worms and sidewinding snakes can be described as modulations of templates. Thus, the use of differential geometry in the locomotion of living systems generates a common description of locomotion across taxa and provides hypotheses for neuromechanical control schemes at lower levels of organization.

Unifying fluidic excretion across life from cicadas to elephants.

Can insects weighing mere grams challenge our current understanding of fluid dynamics in urination, jetting fluids like their larger mammalian counterparts? Current fluid urination models, predominantly formulated for mammals, suggest that jetting is confined to animals over 3 kg, owing to viscous and surface tension constraints at microscales. Our findings defy this paradigm by demonstrating that cicadas-weighing just 2 g-possess the capability for jetting fluids through remarkably small orifices. Using dimensional analysis, we introduce a unifying fluid dynamics scaling framework that accommodates a broad range of taxa, from surface-tension-dominated insects to inertia and gravity-reliant mammals. This study not only refines our understanding of fluid excretion across various species but also highlights its potential relevance in diverse fields such as ecology, evolutionary biology, and biofluid dynamics.

Local volume concentration, packing domains, and scaling properties of chromatin.

We propose the Self Returning Excluded Volume (SR-EV) model for the structure of chromatin based on stochastic rules and physical interactions. The SR-EV rules of return generate conformationally defined domains observed by single-cell imaging techniques. From nucleosome to chromosome scales, the model captures the overall chromatin organization as a corrugated system, with dense and dilute regions alternating in a manner that resembles the mixing of two disordered bi-continuous phases. This particular organizational topology is a consequence of the multiplicity of interactions and processes occurring in the nuclei, and mimicked by the proposed return rules. Single configuration properties and ensemble averages show a robust agreement between theoretical and experimental results including chromatin volume concentration, contact probability, packing domain identification and size characterization, and packing scaling behavior. Model and experimental results suggest that there is an inherent chromatin organization regardless of the cell character and resistant to an external forcing such as RAD21 degradation.

Gendered hiring and attrition on the path to parity for academic faculty.

Despite long-running efforts to increase gender diversity among tenured and tenure-track faculty in the U.S., women remain underrepresented in most academic fields, sometimes dramatically so. Here, we quantify the relative importance of faculty hiring and faculty attrition for both past and future faculty gender diversity using comprehensive data on the training and employment of 268,769 tenured and tenure-track faculty rostered at 12,112U.S. PhD-granting departments, spanning 111 academic fields between 2011 and 2020. Over this time, we find that hiring had a far greater impact on women's representation among faculty than attrition in the majority (90.1%) of academic fields, even as academia loses a higher share of women faculty relative to men at every career stage. Finally, we model the impact of five specific policy interventions on women's representation, and project that eliminating attrition differences between women and men only leads to a marginal increase in women's overall representation-in most fields, successful interventions will need to make substantial and sustained changes to hiring in order to reach gender parity.

Female-dominated disciplines have lower evaluated research quality and funding success rates, for men and women.

We use data from 30 countries and find that the more women in a discipline, the lower quality the research in that discipline is evaluated to be and the lower the funding success rate is. This affects men and women, and is robust to age, number of research outputs, and bibliometric measures where such data are available. Our work builds on others' findings that women's work is valued less, regardless of who performs that work.

There have been growing concerns around sexism in science. Studies have found that women in science are often paid less, are less likely to get credit for their work and receive fewer and smaller grants than men at similar stages in their careers. This can make it harder for women to advance in their careers, resulting in less women than men taking up positions of leadership. There are also gender imbalances between scientific disciplines, with a higher proportion of women working in some fields compared to others. Here, James et al. set out to find whether having more women working in a discipline leads to biases in how the research is evaluated. The team examined four datasets which included information on the research evaluations and funding success of thousands of researchers across 30 different countries. The analysis suggested that scientists working in women-dominated disciplines were less likely to succeed in their grant applications. Their research was also often evaluated as being lower quality compared to researchers working in fields dominated by men. These biases applied to both men and women working in these disciplines. There were not sufficient data to analyse patterns faced by non-binary individuals. The study by James et al. cannot pinpoint a specific cause for these outcomes. However, it suggests that funding organisations should analyse the pattern of successful applications across disciplines and consider taking steps to ensure all disciplines have similar success rates. James et al. also propose that when hiring or making promotions, scientific institutions should take care when comparing researchers across disciplines and ensure there is no built-in assumption that fields dominated by men are intrinsically better.

The exchange dynamics of biomolecular condensates.

A hallmark of biomolecular condensates formed via liquid-liquid phase separation is that they dynamically exchange material with their surroundings, and this process can be crucial to condensate function. Intuitively, the rate of exchange can be limited by the flux from the dilute phase or by the mixing speed in the dense phase. Surprisingly, a recent experiment suggests that exchange can also be limited by the dynamics at the droplet interface, implying the existence of an 'interface resistance'. Here, we first derive an analytical expression for the timescale of condensate material exchange, which clearly conveys the physical factors controlling exchange dynamics. We then utilize sticker-spacer polymer models to show that interface resistance can arise when incident molecules transiently touch the interface without entering the dense phase, i.e., the molecules 'bounce' from the interface. Our work provides insight into condensate exchange dynamics, with implications for both natural and synthetic systems.

Cyclic muscle contractions reinforce the actomyosin motors and mediate the full elongation of C. elegans embryo.

The paramount importance of mechanical forces in morphogenesis and embryogenesis is widely recognized, but understanding the mechanism at the cellular and molecular level remains challenging. Because of its simple internal organization, Caenorhabditis elegans is a rewarding system of study. As demonstrated experimentally, after an initial period of steady elongation driven by the actomyosin network, muscle contractions operate a quasi-periodic sequence of bending, rotation, and torsion, that leads to the final fourfold size of the embryos before hatching. How actomyosin and muscles contribute to embryonic elongation is investigated here theoretically. A filamentary elastic model that converts stimuli generated by biochemical signals in the tissue into driving forces, explains embryonic deformation under actin bundles and muscle activity, and dictates mechanisms of late elongation based on the effects of energy conversion and dissipation. We quantify this dynamic transformation by stretches applied to a cylindrical structure that mimics the body shape in finite elasticity, obtaining good agreement and understanding of both wild-type and mutant embryos at all stages.

Substrate evaporation drives collective construction in termites.

Termites build complex nests which are an impressive example of self-organization. We know that the coordinated actions involved in the construction of these nests by multiple individuals are primarily mediated by signals and cues embedded in the structure of the nest itself. However, to date there is still no scientific consensus about the nature of the stimuli that guide termite construction, and how they are sensed by termites. In order to address these questions, we studied the early building behavior of Coptotermes gestroi termites in artificial arenas, decorated with topographic cues to stimulate construction. Pellet collections were evenly distributed across the experimental setup, compatible with a collection mechanism that is not affected by local topography, but only by the distribution of termite occupancy (termites pick pellets at the positions where they are). Conversely, pellet depositions were concentrated at locations of high surface curvature and at the boundaries between different types of substrate. The single feature shared by all pellet deposition regions was that they correspond to local maxima in the evaporation flux. We can show analytically and we confirm experimentally that evaporation flux is directly proportional to the local curvature of nest surfaces. Taken together, our results indicate that surface curvature is sufficient to organize termite building activity and that termites likely sense curvature indirectly through substrate evaporation. Our findings reconcile the apparently discordant results of previous studies.

The younger flagellum sets the beat for Chlamydomonas reinhardtii.

Eukaryotes swim with coordinated flagellar (ciliary) beating and steer by fine-tuning the coordination. The model organism for studying flagellate motility, Chlamydomonas reinhardtii, employs synchronous, breaststroke-like flagellar beating to swim, and it modulates the beating amplitudes differentially to steer. This strategy hinges on both inherent flagellar asymmetries (e.g. different response to chemical messengers) and such asymmetries being effectively coordinated in the synchronous beating. In C. reinhardtii, the synchrony of beating is known to be supported by a mechanical connection between flagella; however, how flagellar asymmetries persist in the synchrony remains elusive. For example, it has been speculated for decades that one flagellum leads the beating, as its dynamic properties (i.e. frequency, waveform, etc.) appear to be copied by the other one. In this study, we combine experiments, computations, and modeling efforts to elucidate the roles played by each flagellum in synchronous beating. With a non-invasive technique to selectively load each flagellum, we show that the coordinated beating essentially only responds to load exerted on the cis flagellum; and that such asymmetry in response derives from a unilateral coupling between the two flagella. Our results highlight a distinct role for each flagellum in coordination and have implication for biflagellates' tactic behaviors.

Many single-cell organisms use tiny hair-like structures called flagella to move around. To direct this movement, the flagella must work together and beat in a synchronous manner. In some organisms, coordination is achieved by each flagellum reacting to the flow generated by neighbouring flagella. In others, flagella are joined together by fiber connections between their bases, which allow movement to be coordinated through mechanical signals sent between flagella. One such organism is Chlamydomonas reinhardtii, a type of algae frequently used to study flagellar coordination. Its two flagella ­ named trans and cis because of their positions relative to the cell's eyespot ­ propel the cell through water using breaststroke-like movements. To steer, C. reinhardtii adjusts the strength of the strokes made by each flagellum. Despite this asymmetry, the flagella must continue to beat in synchrony to move efficiently. To understand how the cell manages these differences, Wei et al. exposed each flagellum to carefully generated oscillations in water so that each was exposed to different forces and their separate responses could be measured. A combination of experiments, modelling and computer simulations were then used to work out how the two flagella coordinate to steer the cell. Wei et al. found that only the cis flagellum coordinates the beating, with the trans flagellum simply copying the motion of the cis. A direct consequence of such one-way coupling is that only forces on the cis flagellum influence the coordinated beating dynamics of both flagella. These findings shed light on the unique roles of each flagellum in the coordinated movement in C. reinhardtii and have implications for how other organisms with mechanically-connected flagella navigate their environments.

Energy conservation by collective movement in schooling fish.

Many animals moving through fluids exhibit highly coordinated group movement that is thought to reduce the cost of locomotion. However, direct energetic measurements demonstrating the energy-saving benefits of fluid-mediated collective movements remain elusive. By characterizing both aerobic and anaerobic metabolic energy contributions in schools of giant danio (Devario aequipinnatus), we discovered that fish schools have a concave upward shaped metabolism-speed curve, with a minimum metabolic cost at ~1 body length s-1. We demonstrate that fish schools reduce total energy expenditure (TEE) per tail beat by up to 56% compared to solitary fish. When reaching their maximum sustained swimming speed, fish swimming in schools had a 44% higher maximum aerobic performance and used 65% less non-aerobic energy compared to solitary individuals, which lowered the TEE and total cost of transport by up to 53%, near the lowest recorded for any aquatic organism. Fish in schools also recovered from exercise 43% faster than solitary fish. The non-aerobic energetic savings that occur when fish in schools actively swim at high speed can considerably improve both peak and repeated performance which is likely to be beneficial for evading predators. These energetic savings may underlie the prevalence of coordinated group locomotion in fishes.

Schools of fish, flocks of birds flying in a V-formation and other collective movements of animals are common and mesmerizing behaviours. Moving as a group can have many benefits including helping the animals to find food and reproduce and protecting them from predators. Collective movements may also help animals to save energy as they travel by altering the flow of air or water around individuals. Computational models based on the flow of water suggest several possible mechanisms for how fish swimming in schools may use less energy compared to fish swimming on their own. However, few studies have directly measured how much energy fish schools actually use while they swim compared to a solitary individual. Zhang and Lauder used a device called a respirometer to directly measure the energy used by small tropical fish, known as giant danio, swimming in schools and on their own in an aquatic treadmill. The experiments found that the fish swimming in schools used 53% less energy compared with fish swimming on their own, and that fish in schools recovered from a period of high-speed swimming 43% quicker than solitary fish. By adjusting the flow of the water in the tanks, the team were able to study the fish schools swimming at different speeds. This revealed that the fish used more energy when they hovered slowly, or swam fast, than when they swam at a more moderate speed. Previous studies have found that many fish tend to swim at a moderate speed of around one body length per second while they travel long distances. Zhang and Lauder found that the giant danio used the least energy when they swam at this 'migratory' speed. These findings show that swimming in schools can help fish save energy compared with swimming alone. Along with furthering our understanding of how collective movement benefits fish and other animals, this work may help engineers to design robots that can team up with other robots to move more efficiently through the water.

Energetics of the microsporidian polar tube invasion machinery.

Microsporidia are eukaryotic, obligate intracellular parasites that infect a wide range of hosts, leading to health and economic burdens worldwide. Microsporidia use an unusual invasion organelle called the polar tube (PT), which is ejected from a dormant spore at ultra-fast speeds, to infect host cells. The mechanics of PT ejection are impressive. Anncaliia algerae microsporidia spores (3-4 µm in size) shoot out a 100-nm-wide PT at a speed of 300 µm/s, creating a shear rate of 3000 s-1. The infectious cargo, which contains two nuclei, is shot through this narrow tube for a distance of ∼60-140 µm (Jaroenlak et al, 2020) and into the host cell. Considering the large hydraulic resistance in an extremely thin tube and the low-Reynolds-number nature of the process, it is not known how microsporidia can achieve this ultrafast event. In this study, we use Serial Block-Face Scanning Electron Microscopy to capture 3-dimensional snapshots of A. algerae spores in different states of the PT ejection process. Grounded in these data, we propose a theoretical framework starting with a systematic exploration of possible topological connectivity amongst organelles, and assess the energy requirements of the resulting models. We perform PT firing experiments in media of varying viscosity, and use the results to rank our proposed hypotheses based on their predicted energy requirement. We also present a possible mechanism for cargo translocation, and quantitatively compare our predictions to experimental observations. Our study provides a comprehensive biophysical analysis of the energy dissipation of microsporidian infection process and demonstrates the extreme limits of cellular hydraulics.

Quantifying gliding forces of filamentous cyanobacteria by self-buckling.

Filamentous cyanobacteria are one of the oldest and today still most abundant lifeforms on earth, with manifold implications in ecology and economics. Their flexible filaments, often several hundred cells long, exhibit gliding motility in contact with solid surfaces. The underlying force generating mechanism is not yet understood. Here, we demonstrate that propulsion forces and friction coefficients are strongly coupled in the gliding motility of filamentous cyanobacteria. We directly measure their bending moduli using micropipette force sensors, and quantify propulsion and friction forces by analyzing their self-buckling behavior, complemented with analytical theory and simulations. The results indicate that slime extrusion unlikely generates the gliding forces, but support adhesion-based hypotheses, similar to the better-studied single-celled myxobacteria. The critical self-buckling lengths align well with the peaks of natural length distributions, indicating the importance of self-buckling for the organization of their collective in natural and artificial settings.

Hydrodynamics and multiscale order in confluent epithelia.

We formulate a hydrodynamic theory of confluent epithelia: i.e. monolayers of epithelial cells adhering to each other without gaps. Taking advantage of recent progresses toward establishing a general hydrodynamic theory of p-atic liquid crystals, we demonstrate that collectively migrating epithelia feature both nematic (i.e. p = 2) and hexatic (i.e. p = 6) orders, with the former being dominant at large and the latter at small length scales. Such a remarkable multiscale liquid crystal order leaves a distinct signature in the system's structure factor, which exhibits two different power-law scaling regimes, reflecting both the hexagonal geometry of small cells clusters and the uniaxial structure of the global cellular flow. We support these analytical predictions with two different cell-resolved models of epithelia - i.e. the self-propelled Voronoi model and the multiphase field model - and highlight how momentum dissipation and noise influence the range of fluctuations at small length scales, thereby affecting the degree of cooperativity between cells. Our construction provides a theoretical framework to conceptualize the recent observation of multiscale order in layers of Madin-Darby canine kidney cells and pave the way for further theoretical developments.

The ability to sense the environment is heterogeneously distributed in cell populations.

Channel capacity of signaling networks quantifies their fidelity in sensing extracellular inputs. Low estimates of channel capacities for several mammalian signaling networks suggest that cells can barely detect the presence/absence of environmental signals. However, given the extensive heterogeneity and temporal stability of cell state variables, we hypothesize that the sensing ability itself may depend on the state of the cells. In this work, we present an information-theoretic framework to quantify the distribution of sensing abilities from single-cell data. Using data on two mammalian pathways, we show that sensing abilities are widely distributed in the population and most cells achieve better resolution of inputs compared to an 'average cell'. We verify these predictions using live-cell imaging data on the IGFR/FoxO pathway. Importantly, we identify cell state variables that correlate with cells' sensing abilities. This information-theoretic framework will significantly improve our understanding of how cells sense in their environment.

Deep learning for rapid analysis of cell divisions in vivo during epithelial morphogenesis and repair.

Cell division is fundamental to all healthy tissue growth, as well as being rate-limiting in the tissue repair response to wounding and during cancer progression. However, the role that cell divisions play in tissue growth is a collective one, requiring the integration of many individual cell division events. It is particularly difficult to accurately detect and quantify multiple features of large numbers of cell divisions (including their spatio-temporal synchronicity and orientation) over extended periods of time. It would thus be advantageous to perform such analyses in an automated fashion, which can naturally be enabled using deep learning. Hence, we develop a pipeline of deep learning models that accurately identify dividing cells in time-lapse movies of epithelial tissues in vivo. Our pipeline also determines their axis of division orientation, as well as their shape changes before and after division. This strategy enables us to analyse the dynamic profile of cell divisions within the Drosophila pupal wing epithelium, both as it undergoes developmental morphogenesis and as it repairs following laser wounding. We show that the division axis is biased according to lines of tissue tension and that wounding triggers a synchronised (but not oriented) burst of cell divisions back from the leading edge.

Neutrophils actively swell to potentiate rapid migration.

While the involvement of actin polymerization in cell migration is well-established, much less is known about the role of transmembrane water flow in cell motility. Here, we investigate the role of water influx in a prototypical migrating cell, the neutrophil, which undergoes rapid, directed movement to sites of injury, and infection. Chemoattractant exposure both increases cell volume and potentiates migration, but the causal link between these processes are not known. We combine single-cell volume measurements and a genome-wide CRISPR screen to identify the regulators of chemoattractant-induced neutrophil swelling, including NHE1, AE2, PI3K-gamma, and CA2. Through NHE1 inhibition in primary human neutrophils, we show that cell swelling is both necessary and sufficient for the potentiation of migration following chemoattractant stimulation. Our data demonstrate that chemoattractant-driven cell swelling complements cytoskeletal rearrangements to enhance migration speed.

Long-distance electron transport in multicellular freshwater cable bacteria.

Filamentous multicellular cable bacteria perform centimeter-scale electron transport in a process that couples oxidation of an electron donor (sulfide) in deeper sediment to the reduction of an electron acceptor (oxygen or nitrate) near the surface. While this electric metabolism is prevalent in both marine and freshwater sediments, detailed electronic measurements of the conductivity previously focused on the marine cable bacteria (Candidatus Electrothrix), rather than freshwater cable bacteria, which form a separate genus (Candidatus Electronema) and contribute essential geochemical roles in freshwater sediments. Here, we characterize the electron transport characteristics of Ca. Electronema cable bacteria from Southern California freshwater sediments. Current-voltage measurements of intact cable filaments bridging interdigitated electrodes confirmed their persistent conductivity under a controlled atmosphere and the variable sensitivity of this conduction to air exposure. Electrostatic and conductive atomic force microscopies mapped out the characteristics of the cell envelope's nanofiber network, implicating it as the conductive pathway in a manner consistent with previous findings in marine cable bacteria. Four-probe measurements of microelectrodes addressing intact cables demonstrated nanoampere currents up to 200 µm lengths at modest driving voltages, allowing us to quantify the nanofiber conductivity at 0.1 S/cm for freshwater cable bacteria filaments under our measurement conditions. Such a high conductivity can support the remarkable sulfide-to-oxygen electrical currents mediated by cable bacteria in sediments. These measurements expand the knowledgebase of long-distance electron transport to the freshwater niche while shedding light on the underlying conductive network of cable bacteria.

Combining mutation and recombination statistics to infer clonal families in antibody repertoires.

B-cell repertoires are characterized by a diverse set of receptors of distinct specificities generated through two processes of somatic diversification: V(D)J recombination and somatic hypermutations. B-cell clonal families stem from the same V(D)J recombination event, but differ in their hypermutations. Clonal families identification is key to understanding B-cell repertoire function, evolution, and dynamics. We present HILARy (high-precision inference of lineages in antibody repertoires), an efficient, fast, and precise method to identify clonal families from single- or paired-chain repertoire sequencing datasets. HILARy combines probabilistic models that capture the receptor generation and selection statistics with adapted clustering methods to achieve consistently high inference accuracy. It automatically leverages the phylogenetic signal of shared mutations in difficult repertoire subsets. Exploiting the high sensitivity of the method, we find the statistics of evolutionary properties such as the site frequency spectrum and dN/dS ratio do not depend on the junction length. We also identify a broad range of selection pressures spanning two orders of magnitude.

Pump up the volume.

An influx of water molecules can help immune cells called neutrophils to move to where they are needed in the body.

Fluid ejections in nature.

From microscopic fungi to colossal whales, fluidic ejections are a universal and intricate phenomenon in biology, serving vital functions such as animal excretion, venom spraying, prey hunting, spore dispersal, and plant guttation. This review delves into the complex fluid physics of ejections across various scales, exploring both muscle-powered active systems and passive mechanisms driven by gravity or osmosis. We introduce a framework using dimensionless numbers to delineate transitions from dripping to jetting and elucidate the governing forces. Highlighting the understudied area of complex fluid ejections, this work not only rationalizes the biophysics involved but also uncovers potential engineering applications in soft robotics, additive manufacturing, and drug delivery. By bridging biomechanics, the physics of living systems, and fluid dynamics, this review offers valuable insights into the diverse world of fluid ejections and paves the way for future bioinspired research across the spectrum of life.