eLife: latest articles by subject

Collective epithelial migration mediated by the unbinding of hexatic defects

giomi@lorentz.leidenuniv.nl (Dimitrios Krommydas) — Tue, 05 May 2026 00:00:00 +0000

Collective cell migration in epithelia relies on cell intercalation: a local remodeling of the cellular network that allows neighboring cells to swap their positions. Unlike foams and passive cellular fluid, in epithelial intercalation, these rearrangements crucially depend on activity. During these processes, the local geometry of the network and the contractile forces generated therein conspire to produce a burst of remodeling events, which collectively give rise to a vortical flow at the mesoscopic length scale. In this article, we formulate a continuum theory of the mechanism driving this process, built upon recent advances toward understanding the hexatic (i.e., sixfold ordered) structure of epithelial layers. Using a combination of active hydrodynamics and cell-resolved numerical simulations, we demonstrate that cell intercalation takes place via the unbinding of topological defects, naturally initiated by fluctuations and whose late-times dynamics is governed by the interplay between passive attractive forces and active self-propulsion. Our approach sheds light on the structure of the cellular forces driving collective migration in epithelia and provides an explanation of the observed extensile activity of in vitro epithelial layers.

Colony demographics shape nest construction in Camponotus fellah ants

ofer.feinerman@weizmann.ac.il (Ehud Fonio) — Wed, 22 Apr 2026 00:00:00 +0000

The ant nest serves as the skeleton of the ant superorganism. Similar to a skeleton, the nest expands as the colony grows and requires repair after catastrophic events. We experimentally compared nest excavation in colonies seeded from a single mated queen and allowed to grow for 6 months to excavation triggered by a catastrophic event in colonies with fixed demographics, where the age of each worker, including the queen, is known. The areas excavated by equal group sizes differed significantly between these conditions: heterogeneous populations in naturally growing colonies as well as cohorts of young ants dig larger areas than old ant cohorts. Moreover, we find that younger ants tend to dig slanted tunnels while older ants dig straight down. This is a novel form of age polyethism, where an ant’s age dictates not only her likelihood to engage in a task but also the way she performs the task. We further present a quantitative model that predicts that under normal growth, digging is predominantly performed by the younger ants, while after a catastrophe, all ants dig to restore lost nest volume. The fact that the nests of naturally growing colonies exhibit slanted tunnels strengthens this prediction. Finally, our results indicate how a colony’s demographic and physical history are sketched into the current structure of its nest.

Fragmentation and aggregation of cyanobacterial colonies

y.z.sinzato@uva.nl (Jef Huisman) — Fri, 17 Apr 2026 00:00:00 +0000

Fluid flow has a major effect on the aggregation and fragmentation of bacterial colonies. Yet, a generic framework to understand and predict how hydrodynamics affects colony size remains elusive. This study investigates how fluid flow affects the formation and maintenance of large colonial structures in cyanobacteria, using an experimental technique that precisely controls hydrodynamic conditions. We performed experiments on laboratory cultures and lake samples of the cyanobacterium Microcystis, while their colony size distribution was measured simultaneously by direct microscopic imaging. We demonstrate that extracellular polymeric substances (EPS)-embedded cells formed by cell division exhibit significant mechanical resistance to shear forces. However, at elevated hydrodynamic stress levels (exceeding those typically generated by surface wind mixing), these colonies experience fragmentation through an erosion process. We also show that single cells can aggregate into small colonies due to fluid flow. However, the structural integrity of these flow-induced colonies is weaker than that of colonies formed by cell division. We provide a mathematical analysis to support the experiments and demonstrate that a population model with two categories of colonies describes the measured size distributions. Our results shed light on the specific conditions wherein flow-induced fragmentation and aggregation of cyanobacteria are decisive and indicate that colony formation under natural conditions is mainly driven by cell division, although flow-induced aggregation could play a role in dense bloom events. These findings can be used to improve prediction models and mitigation strategies for toxic cyanobacterial blooms and also offer potential applications in other areas, such as algal biotechnology or medical settings where the dynamics of biological aggregates play a significant role.

Revealing global stoichiometry conservation architecture in cells from Raman spectral patterns

kenichiro_kamei@cell.c.u-tokyo.ac.jp (Hidenori Nakaoka) — Tue, 14 Apr 2026 00:00:00 +0000

Cells can adapt to various environments by changing their biomolecular profiles while maintaining physiological homeostasis. What organizational principles in cells enable the simultaneous realization of adaptability and homeostasis? To address this question, we measure Raman scattering light from Escherichia coli cells under diverse conditions, whose spectral patterns convey their comprehensive molecular composition. We reveal that dimension-reduced Raman spectra can predict condition-dependent proteome profiles. Quantitative analysis of the Raman-proteome correspondence characterizes a low-dimensional hierarchical stoichiometry-conserving proteome structure. The network centrality of each gene in the stoichiometry conservation relations correlates with its essentiality and evolutionary conservation, and these correlations are preserved from bacteria to human cells. Furthermore, stoichiometry-conserving core components obey growth law and ensure homeostasis across conditions, whereas peripheral stoichiometry-conserving components enable adaptation to specific conditions. Mathematical analysis reveals that the stoichiometrically constrained architecture is reflected in major changes in Raman spectral patterns. These results uncover coordination of global stoichiometric balance in cells and demonstrate that vibrational spectroscopy can decipher such biological constraints beyond statistical or machine-learning inference of cellular states.

Enhanced bacterial chemotaxis in confined microchannels occurs at lane widths matching circular swimming radius

zhchi@ustc.edu.cn (Caijuan Yue) — Tue, 14 Apr 2026 00:00:00 +0000

Understanding bacterial behavior in confined environments is helpful for elucidating microbial ecology and developing strategies to manage bacterial infections. While extensive research has focused on bacterial motility on surfaces and in porous media, chemotaxis in confined spaces remains poorly understood. Here, we investigate the chemotaxis of Escherichia coli within microfluidic lanes under a linear concentration gradient of L-aspartate. We demonstrate that E. coli exhibits significantly enhanced chemotaxis in lanes with sidewalls compared to open surfaces. We attribute this phenomenon primarily to the intrinsic chiral clockwise circular motion of surface-swimming bacteria and the subsequent alignment effect upon collision with the sidewalls. By varying lane widths, we identify that an 8 μm width—approximating the radius of bacterial circular swimming on surfaces—maximizes chemotactic drift velocity. These results are supported by both experimental observations and stochastic simulations, establishing a clear proportional relationship between optimal lane width and the radius of bacterial circular swimming. Further geometric analysis provides an intuitive understanding of this phenomenon. Our results may offer insights into bacterial navigation in complex biological environments such as host tissues and biofilms, providing a preliminary step toward exploring microbial ecology in confined habitats and potential strategies for controlling bacterial infections.

Detecting directed motion and confinement in single-particle trajectories using hidden variables

simon.francois@protonmail.com (Caroline Boudoux) — Tue, 07 Apr 2026 00:00:00 +0000

Single-particle tracking is a powerful tool for understanding protein dynamics and characterizing microenvironments. As the motion of unconstrained nanoscale particles is governed by Brownian diffusion, deviations from this behavior are biophysically insightful. However, the stochastic nature of particle movement and the presence of localization error pose a challenge for the robust classification of non-Brownian motion. Here, we present aTrack, a versatile tool for classifying track behaviors and extracting key parameters for particles undergoing Brownian, confined, or directed motion. Our tool quickly and accurately estimates motion parameters from individual tracks. Further, our tool can analyze populations of tracks and determine the most likely number of motion states. We show the working range of our approach on simulated tracks and demonstrate its application for characterizing particle motion in Saccharomyces cerevisiae and for biosensing applications in Escherichia coli. aTrack is implemented as a stand-alone software, making it simple to analyze track data.

A deep learning pipeline for mapping in situ network-level neurovascular coupling in multi-photon fluorescence microscopy

maged.goubran@utoronto.ca (Adrienne Dorr) — Tue, 24 Mar 2026 00:00:00 +0000

Functional hyperemia is a well-established hallmark of healthy brain function, whereby local brain blood flow adjusts in response to a change in the activity of the surrounding neurons. Although functional hyperemia has been extensively studied at the level of both tissue and individual vessels, vascular network-level coordination remains largely unknown. To bridge this gap, we developed a deep learning-based pipeline that uses two-photon fluorescence microscopy images of cerebral microcirculation to enable automated reconstruction and quantification of the geometric changes across the microvascular network, comprising hundreds of interconnected blood vessels, pre and post-activation of the neighboring neurons. The pipeline’s utility was demonstrated in the Thy1-ChR2 optogenetic mouse model, where we observed network-wide vessel radius changes to depend on the photostimulation intensity, with both dilations and constrictions occurring across the cortical depth, at an average of 16.1±14.3 μm (mean ± SD) away from the most proximal neuron for dilations; and at 21.9±14.6 μm away for constrictions. We observed a significant heterogeneity of the vascular radius changes within vessels, with radius adjustment varying by an average of 24 ± 28% of the resting diameter, likely reflecting the heterogeneity of the distribution of contractile cells on the vessel walls. A graph theory-based network analysis revealed that the assortativity of adjacent blood vessel responses rose by 152 ± 65% at 4.3 mW/mm² of blue photostimulation vs. the control, with a 4% median increase in the efficiency of the capillary networks during this level of blue photostimulation in relation to the baseline. Interrogating individual vessels is thus not sufficient to predict how the blood flow is modulated in the network. Our pipeline, enables tracking of the microvascular network geometry over time, relating caliber adjustments to vessel wall-associated cells’ state, and mapping network-level flow distribution impairments in experimental models of disease.

The cytoplasm of living cells can sustain transient and steady intracellular pressure gradients

m.malboubi@bham.ac.uk (Emad Moeendarbary) — Mon, 23 Mar 2026 00:00:00 +0000

Understanding the physical basis of cellular shape change in response to both internal and external mechanical stresses requires characterisation of cytoplasmic rheology. At subsecond time-scales and micron length-scales, cells behave as fluid-filled sponges in which shape changes necessitate intracellular fluid redistribution. However, whether these cytoplasmic poroelastic properties play an important role in cellular mechanical response over length- and time-scales relevant to cell physiology remains unclear. Here, we investigated whether and how a localised deformation of the cell surface gives rise to transient intracellular flows spanning several microns and lasting seconds. Next, we showed that pressure gradients induced in the cytoplasm can be sustained over several minutes. We found that stable pressure gradients can arise from the combination of cortical tension, cytoplasmic poroelasticity, and water flows across the membrane. Overall our data indicate that intracellular cytosolic flows and pressure gradients may play a much greater role than currently appreciated, acting over time- and length-scales relevant to mechanotransduction and cell migration, signifying that poroelastic properties need to be accounted for in models of the cell.

Feeding rates in sessile versus motile ciliates are hydrodynamically equivalent

kanso@usc.edu (Eva Kanso) — Thu, 29 Jan 2026 00:00:00 +0000

Motility endows microorganisms with the ability to swim to nutrient-rich environments, but many species are sessile. Existing hydrodynamic arguments in support of either strategy, to swim or to attach and generate feeding currents, are often built on a limited set of experimental or modeling assumptions. Here, to assess the hydrodynamics of these ‘swim’ or ‘stay’ strategies, we propose a comprehensive methodology that combines mechanistic modeling with a survey of published shape and flow data in ciliates. Model predictions and empirical observations show small variations in feeding rates in favor of either motile or sessile cells. Case-specific variations notwithstanding, our overarching analysis shows that flow physics imposes no constraint on the feeding rates that are achievable by the swimming versus sessile strategies – they can both be equally competitive in transporting nutrients and wastes to and from the cell surface within flow regimes typically experienced by ciliates. Our findings help resolve a long-standing dilemma of which strategy is hydrodynamically optimal and explain patterns occurring in natural communities that alternate between free swimming and temporary attachments. Importantly, our findings indicate that the evolutionary pressures that shaped these strategies acted in concert with, not against, flow physics.

Robust assessment of asymmetric division in colon cancer cells

mattia.miotto@roma1.infn.it (Chiara Giannattasio) — Fri, 23 Jan 2026 00:00:00 +0000

Asymmetric partition of fate determinants during cell division is a hallmark of cell differentiation. Recent work suggested that such a mechanism is hijacked by cancer cells to increase both their phenotypic heterogeneity and plasticity and, in turn, their fitness. To quantify fluctuations in the partitioning of cellular elements, imaging-based approaches are used, whose accuracy is limited by the difficulty of detecting cell divisions. Our work addresses this gap, proposing a general method based on high-throughput flow cytometry measurements coupled with a theoretical framework. We applied our method to a panel of both normal and cancerous human colon cells, showing that different kinds of colon adenocarcinoma cells display very distinct extents of fluctuations in their cytoplasm partition, explained by an asymmetric division of their size. To test the accuracy of our population-level protocol, we directly measure the inherited fractions of cellular elements from extensive time lapses of live-cell laser scanning microscopy, finding excellent agreement across the cell types. Ultimately, our flow cytometry-based method promises to be accurate and easily applicable to a wide range of biological systems where the quantification of partition fluctuations would help account for the observed phenotypic heterogeneity and plasticity.

Linking complex microbial interactions and dysbiosis through a disordered Lotka–Volterra model

ada.altieri@u-paris.fr (Ada Altieri) — Mon, 12 Jan 2026 00:00:00 +0000

The rapid advancement of environmental sequencing technologies, such as metagenomics, has significantly enhanced our ability to study microbial communities. The eubiotic composition of these communities is crucial for maintaining ecological functions and host health. Species diversity is only one facet of a healthy community’s organization; together with abundance distributions and interaction structures, it shapes reproducible macroecological states, that is, joint statistical fingerprints that summarize whole-community behavior. Despite recent developments, a theoretical framework connecting empirical data with ecosystem modeling is still in its infancy, particularly in the context of disordered systems. Here, we present a novel framework that couples statistical physics tools for disordered systems with metagenomic data, explicitly linking diversity, interactions, and stability to define and compare these macroecological states. By employing the generalized Lotka–Volterra model with random interactions, we reveal two different emergent patterns of species interaction networks and species abundance distributions for healthy and diseased microbiomes. On the one hand, healthy microbiomes have similar community structures across individuals, characterized by strong species interactions and abundance diversity consistent with neutral stochastic fluctuations. On the other hand, diseased microbiomes show greater variability driven by deterministic factors, thus resulting in less ecologically stable and more divergent communities. Our findings suggest the potential of disordered system theory to characterize microbiomes and to capture the role of ecological interactions on stability and functioning.

Probing the proteome

whl243@as.edu.tw (Chia-Liang Cheng) — Wed, 07 Jan 2026 00:00:00 +0000

Raman spectroscopy can be used to predict cellular physiology and proteome composition in E. coli.

Atypical collective oscillatory activity in cardiac tissue uncovered by optogenetics

a.teplenin@lumc.nl (Alexander S Teplenin) — Wed, 07 Jan 2026 00:00:00 +0000

Many biological processes emerge as frequency-dependent responses to trains of external stimuli. Heart rhythm disturbances, that is cardiac arrhythmias, are important examples as they are often triggered by specific patterns of preceding stimuli. In this study, we investigated how ectopic arrhythmias can be induced by external stimuli in cardiac tissue containing a localised area of depolarisation. Using optogenetic in vitro experiments and in silico modelling, we systematically explored the dynamics of these arrhythmias, which are characterised by local oscillatory activity, by gradually altering the degree of depolarisation in a predefined region. Our findings reveal a bi-stable system, in which transitions between oscillatory ectopic activity and a quiescent state can be precisely controlled, that is by adjusting the number and frequency of propagating waves through the depolarised area oscillations could be turned on or off. These frequency-dependent responses arise from collective mechanisms involving stable, non-self-oscillatory cells, contrasting with the typical role of self-oscillations in individual units within biophysical systems. To further generalise these findings, we demonstrated similar frequency selectivity and bi-stability in a simplified reaction–diffusion model. This suggests that complex ionic cell dynamics are not required to reproduce these effects; rather, simpler non-linear systems can replicate similar behaviour, potentially extending beyond the cardiac context.

The evolution of interdisciplinarity and internationalization in scientific journals

amaral@northwestern.edu (Huaxia Zhou) — Wed, 31 Dec 2025 00:00:00 +0000

There is a widely held perception that science is becoming more international—through multi-national collaborations—and interdisciplinary, drawing on knowledge from multiple domains. However, these hypothesized trends have not yet been quantitatively characterized. With the publication metadata from OpenAlex, we examine trends in two groups of journals: disciplinary journals in natural sciences, life sciences, social sciences, and multidisciplinary journals that publish articles in multiple fields. Supporting existing perceptions, we find an almost universal trend towards increasing internationalization of both sets of journals. Nevertheless, we find disparities: medicine journals are less international than journals in other disciplines and do not increase their levels of internationalization, whereas physics journals appear to be segregating between those that are international and those that are not. We also find that multidisciplinary journals have undergone significant shifts in their disciplinary focuses over the past century, whereas disciplinary journals appear to have largely maintained their degree of interdisciplinarity.

Postural adaptations may contribute to the unique locomotor energetics seen in hopping kangaroos

cclement@usc.edu.au (Alexis Wiktorowicz-Conroy) — Tue, 16 Dec 2025 00:00:00 +0000

Hopping kangaroos exhibit remarkably little change in their rate of metabolic energy expenditure with locomotor speed compared to other running animals. This phenomenon may be related to greater elastic energy savings due to increasing tendon stress; however, the mechanisms which enable the rise in stress without additional muscle work remain poorly understood. In this study, we created a three-dimensional (3D) kangaroo musculoskeletal model, integrating 3D motion capture and force plate data, to analyse the kinematics and kinetics of hopping red and grey kangaroos. Using our model, we evaluated how body mass and speed influence (i) hindlimb posture, (ii) effective mechanical advantage (EMA), (iii) the associated tendon stress in the ankle extensors, and (iv) ankle work during hopping. We found that increasing ankle dorsiflexion and metatarsophalangeal plantarflexion likely played an important role in decreasing ankle EMA by altering both the muscle and external moment arms, which subsequently increased energy absorption and peak tendon stress at the ankle. Surprisingly, kangaroo hindlimb posture changes appeared to contribute to increased tendon stress, allowing more elastic energy storage at faster speeds. These posture-mediated increases in elastic energy storage and return could be a key factor enabling kangaroos to achieve energetic benefits at faster hopping speeds, but may limit the performance of large kangaroos due to the risk of tendon rupture.

Exploiting fluctuations in gene expression to detect causal interactions between genes

andreas.hilfinger@utoronto.ca (Andreas Hilfinger) — Tue, 16 Dec 2025 00:00:00 +0000

Characterizing and manipulating cellular behavior requires a mechanistic understanding of the causal interactions between cellular components. We present an approach to detect causal interactions between genes without the need to perturb the physiological state of cells. This approach exploits naturally occurring cell-to-cell variability which is experimentally accessible from static population snapshots of genetically identical cells without the need to follow cells over time. Our main contribution is a simple mathematical relation that constrains the propagation of gene expression noise through biochemical reaction networks. This relation allows us to rigorously interpret fluctuation data even when only a small part of a complex gene regulatory process can be observed. We show how this relation can, in theory, be exploited to detect causal interactions by synthetically engineering a passive reporter of gene expression, akin to the established ‘dual reporter assay’. While the focus of our contribution is theoretical, we also present an experimental proof-of-principle to demonstrate the real-world applicability of our approach in certain circumstances. Our experimental data suggest that the method can detect causal interactions in specific synthetic gene regulatory circuits in Escherichia coli, confirming our theoretical result in a narrow set of controlled experimental settings. Further work is needed to show that the approach is practical on a large scale, with naturally occurring gene regulatory networks, or in organisms other than E. coli.

Advantageous and disadvantageous inequality aversion can be taught through learning of others’ preferences

shen.zhang@mail.bnu.edu.cn (A Ross Otto) — Thu, 11 Dec 2025 00:00:00 +0000

While enforcing egalitarian social norms is critical for human society, punishing social norm violators often incurs a cost to the self. This cost looms even larger when one can benefit from an unequal distribution of resources, a phenomenon known as advantageous inequity—for example, receiving a higher salary than a colleague with the identical role. In the Ultimatum Game, a classic testbed for fairness norm enforcement, individuals rarely reject (or punish) such unequal proposed divisions of resources because doing so entails a sacrifice of one’s own benefit. Recent work has demonstrated that observing and implementing another’s punitive responses to unfairness can efficiently alter the punitive preferences of an observer. It remains an open question, however, whether such contagion is powerful enough to impart advantageous inequity aversion to individuals—that is, can observing another’s preferences to punish inequity result in increased enforcement of equality norms, even in the difficult case of Advantageous inequity? Using a variant of the Ultimatum Game in which participants are tasked with responding to fairness violations on behalf of another ‘Teacher’—whose aversion to advantageous (versus disadvantageous) inequity was systematically manipulated—we probe whether individuals subsequently increase their punishment unfairly after experiencing fairness violations on their own behalf. In two experiments, we found individuals can acquire aversion to advantageous inequity through observing (and implementing) the Teacher’s preferences. Computationally, these learning effects were best characterized by a model which learns the latent structure of the Teacher’s preferences, rather than a simple Reinforcement Learning account. In summary, our study is the first to demonstrate that people can swiftly and readily acquire another’s preferences for advantageous inequity, suggesting in turn that behavioral contagion may be one promising mechanism through which social norm enforcement—which people rarely implement in the case of advantageous inequality—can be enhanced.

Theory of active self-organization of dense nematic structures in the actin cytoskeleton

alejandro.torressanchez@embl.es (Alejandro Torres-Sánchez) — Mon, 08 Dec 2025 00:00:00 +0000

The actin cytoskeleton is remarkably adaptable and multifunctional. It often organizes into nematic bundles such as contractile rings or stress fibers. However, how a uniform and isotropic actin gel self-organizes into dense nematic bundles is not fully understood. Here, using an active gel model accounting for nematic order and density variations, we identify an active patterning mechanism leading to localized dense nematic structures. Linear stability analysis and nonlinear finite element simulations establish the conditions for nematic bundle self-assembly and how active gel parameters control the architecture, orientation, connectivity, and dynamics of self-organized patterns. Finally, we substantiate with discrete network simulations the main requirements for nematic bundle formation according to our theory, namely increased active tension perpendicular to the nematic direction and generalized active forces conjugate to nematic order. Our work portrays actin gels as reconfigurable active materials with a spontaneous tendency to develop patterns of dense nematic bundles.

Sub-surface deformation of individual fingerprint ridges during tactile interactions

gcorniani@mgh.harvard.edu (Benoit P Delhaye) — Thu, 04 Dec 2025 00:00:00 +0000

The human fingertip can detect small tactile features with a spatial acuity roughly the width of a fingerprint ridge. However, how individual ridges deform under contact to support accurate and high-precision tactile feedback is currently unknown. The complex mechanical structure of the glabrous skin, composed of multiple layers and intricate morphology within which mechanoreceptors are embedded, makes this question challenging. Here, we used optical coherence tomography to image and track sub-surface deformations of hundreds of individual fingerprint ridges across ten participants and four individual contact events at high spatial resolution in vivo. We calculated strain patterns in both the stratum corneum and viable epidermis in response to a variety of passively applied tactile stimuli, including static indentation, stick-to-slip events, sliding of a flat surface in different directions, and interaction with small tactile features, such as edges and grooves. We found that ridges could stretch, compress, and undergo considerable shearing orthogonal to the skin surface, but there was limited horizontal shear. Therefore, it appears that the primary components of ridge deformation and, potentially, neural responses are deformations of the ridge flanks and their relative movement, rather than overall bending of the ridges themselves. We conclude that the local distribution of mechanoreceptors across the ridges might be ideally suited to extract the resulting strain gradients and that the fingertip skin may possess a higher mechanical spatial resolution than that of a single ridge.

Quantifying the shape of cells, from Minkowski tensors to p-atic orders

axel.voigt@tu-dresden.de (Amin Doostmohammadi) — Wed, 19 Nov 2025 00:00:00 +0000

P-atic liquid crystal theories offer new perspectives on how cells self-organize and respond to mechanical cues. Understanding and quantifying the underlying orientational orders is, therefore, essential for unraveling the physical mechanisms that govern tissue dynamics. Due to the deformability of cells this requires quantifying their shape. We introduce rigorous mathematical tools and a reliable framework for such shape analysis. Applying this to segmented cells in MDCK monolayers and computational approaches for active vertex models and multiphase field models allows to demonstrate independence of shape measures and the presence of various p-atic orders at the same time. This challenges previous findings and opens new pathways for understanding the role of orientational symmetries and p-atic liquid crystal theories in tissue mechanics and development.

Repeated vaccination with homologous influenza hemagglutinin broadens human antibody responses to unmatched flu viruses

arupc@mit.edu (Aaron G Schmidt) — Thu, 13 Nov 2025 00:00:00 +0000

The ongoing diversification of influenza virus necessitates annual vaccine updating. The vaccine antigen, the viral spike protein hemagglutinin (HA), tends to elicit strain-specific neutralizing activity, predicting that sequential immunization with the same HA strain will boost antibodies with narrow coverage. However, repeated vaccination with homologous SARS-CoV-2 vaccine eventually elicits neutralizing activity against highly unmatched variants, questioning this immunological premise. We evaluated a longitudinal influenza vaccine cohort, where each year the subjects received the same, novel H1N1 2009 pandemic vaccine strain. Repeated vaccination gradually enhanced receptor-blocking antibodies (HAI) to highly unmatched H1N1 strains within individuals with no initial memory recall against these historical viruses. An in silico model of affinity maturation in germinal centers (GCs) integrated with a model of differentiation and expansion of memory cells outside GCs during a recall response provides insight into the potential mechanisms underlying these results and shows how repeated exposure to the same immunogen can broaden the antibody response against diversified targets.

Roles of the membrane-binding motif and the C-terminal domain of RNase E in localization and diffusion in E. coli

emad@illinois.edu (Brooke Ramsey) — Fri, 07 Nov 2025 00:00:00 +0000

In Escherichia coli, RNase E, a central enzyme in RNA processing and mRNA degradation, contains a catalytic N-terminal domain, a membrane-targeting sequence (MTS), and a C-terminal domain (CTD). We investigated how MTS and CTD influence RNase E localization, diffusion, and function. Super-resolution microscopy revealed that ~93% of RNase E localizes to the inner membrane and exhibits slow diffusion similar to polysomes. Comparing the native amphipathic MTS with a transmembrane motif showed that the MTS confers slower diffusion and stronger membrane binding. The CTD further slows diffusion by increasing mass but unexpectedly weakens membrane association. RNase E mutants with partial cytoplasmic localization displayed enhanced co-transcriptional degradation of lacZ mRNA. These findings indicate that variations in the MTS and the presence of the CTD shape the spatiotemporal organization of RNA processing in bacterial cells, providing mechanistic insight into how RNase E domain architecture influences its cellular function.

Non-equilibrium strategies enabling ligand specificity by signaling receptors

andrew.goetz@yale.edu (Andrew Goetz) — Wed, 29 Oct 2025 00:00:00 +0000

Signaling receptors often encounter multiple ligands and have been shown to respond selectively to generate appropriate, context-specific outcomes. At thermal equilibrium, ligand specificity is limited by the relative affinities of ligands for their receptors. Here, we present a non-equilibrium model in which receptors overcome thermodynamic constraints to preferentially signal from specific ligands while suppressing others. In our model, multi-site phosphorylation and active receptor degradation act in concert to regulate ligand specificity, with receptor degradation, a common motif in eukaryotes, providing a previously under-appreciated layer of control. Here, ligand-bound receptors undergo sequential phosphorylation, with progression restarted by ligand unbinding or receptor turnover. High-affinity complexes are kinetically sorted toward degradation-prone states, while low-affinity complexes are sorted toward inactivated states, both limiting signaling. As a result, network activity is maximized for ligands with intermediate affinities. This mechanism explains paradoxical experimental observations in receptor tyrosine kinase signaling, including non-monotonic dependence of signaling output on ligand affinity and kinase activity. Given the ubiquity of multi-site phosphorylation and ligand-induced degradation across signaling receptors, we propose that kinetic sorting may be a general non-equilibrium ligand-discrimination strategy used by multiple signaling receptors.

Toward stable replication of genomic information in pools of RNA molecules

gerland@tum.de (Ludwig Burger) — Thu, 23 Oct 2025 00:00:00 +0000

The transition from prebiotic chemistry to living systems requires the emergence of a scheme for enzyme-free genetic replication. Here, we analyze a recently proposed prebiotic replication scenario, the so-called Virtual Circular Genome (VCG) [Zhou et al., RNA 27, 1-11 (2021)]: Replication takes place in a pool of oligomers, where each oligomer contains a subsequence of a circular genome, such that the oligomers encode the full genome collectively. While the sequence of the circular genome may be reconstructed based on long oligomers, monomers and short oligomers merely act as replication feedstock. We observe a competition between the predominantly error-free ligation of a feedstock molecule to a long oligomer and the predominantly erroneous ligation of two long oligomers. Increasing the length of long oligomers and reducing their concentration decreases the fraction of erroneous ligations, enabling high-fidelity replication in the VCG. Alternatively, the formation of erroneous products can be suppressed if each ligation involves at least one monomer, while ligations between two long oligomers are effectively prevented. This kinetic discrimination (favoring monomer incorporation over oligomer–oligomer ligation) may be an intrinsic property of the activation chemistry, or can be externally imposed by selectively activating only monomers in the pool. Surprisingly, under these conditions, shorter oligomers are extended by monomers more quickly than long oligomers, a phenomenon that has already been observed experimentally [Ding et al., JACS 145, 7504-7515 (2023)]. Our work provides a theoretical explanation for this behavior and predicts its dependence on system parameters such as the concentration of long oligomers. Taken together, the VCG constitutes a promising scenario of prebiotic information replication: It could mitigate challenges in non-enzymatic copying via template-directed polymerization, such as short lengths of copied products and high error rates.

Correction: Emergent periodicity in the collective synchronous flashing of fireflies

Wed, 15 Oct 2025 00:00:00 +0000

Balancing stability and flexibility when reshaping archaeal membranes

andela.saric@ist.ac.at (Anđela Šarić) — Tue, 07 Oct 2025 00:00:00 +0000

Cellular membranes differ across the tree of life. In most bacteria and eukaryotes, single-headed lipids self-assemble into flexible bilayer membranes. By contrast, thermophilic archaea tend to possess bilayer lipids together with double-headed, monolayer spanning bolalipids, which are thought to enable cells to survive in harsh environments. Here, using a minimal computational model for bolalipid membranes, we explore the trade-offs at play when forming membranes. We find that flexible bolalipids form membranes that resemble bilayer membranes because they are able to assume a U-shaped conformation. Conversely, rigid bolalipids, which resemble the bolalipids with cyclic groups found in thermophilic archaea, take on a straight conformation and form membranes that are stiff and prone to pore formation when they undergo changes in shape. Strikingly, however, the inclusion of small amounts of bilayer lipids in a bolalipid membrane is enough to achieve fluid bolalipid membranes that are both stable and flexible, resolving this trade-off. Our study suggests a mechanism by which archaea can tune the material properties of their membranes as and when required to enable them to survive in harsh environments and to undergo essential membrane remodelling events like cell division.

Adaptations in wing morphology rather than wingbeat kinematics enable flight in small hoverfly species

camille.leroy@wur.nl (Camille Le Roy) — Tue, 30 Sep 2025 00:00:00 +0000

Due to physical scaling laws, size greatly affects animal locomotor ability and performance. Whether morphological and kinematic traits always jointly respond to size variation remains poorly known. Here, we examine the relative importance of morphological and kinematic changes in mitigating the consequence of size reduction on aerodynamic force production for weight support, focusing on the flight of hoverflies (Syrphidae). We compared the morphology of 28 hoverfly species, and the flight biomechanics and aerodynamics of eight species with body masses ranging from 5 to 100 mg. Our study reveals no significant effect of body mass on wingbeat kinematics among species, suggesting that morphological rather than kinematics changes compensate for the reduction in weight support associated with an isometric reduction in wing size. Computational fluid dynamics simulations confirmed that adaptations in wing morphology drive the ability of small hoverfly species to generate weight support, although variations in wingbeat kinematics among species cannot be entirely ignored. We show that smaller hoverflies have evolved relatively larger wings and aerodynamically more effective wing shapes, mitigating the reduction in aerodynamic weight support associated with isometric size reduction. Altogether, these results suggest that hoverfly flight underpins highly specialised wingbeat kinematics, largely conserved throughout evolution; instead, evolutionary adaptations in wing morphology enabled flight of small hoverflies.

Design principles of transcription factors with intrinsically disordered regions

wencheng.ji@weizmann.ac.il (Ariel Amir) — Tue, 30 Sep 2025 00:00:00 +0000

Transcription factors (TFs) are proteins crucial for regulating gene expression. Effective regulation requires the TFs to rapidly bind to their correct target, enabling the cell to respond efficiently to stimuli such as nutrient availability or the presence of toxins. However, the search process is hindered by slow diffusive movement and the presence of ‘false’ targets – DNA segments that are similar to the true target. In eukaryotic cells, most TFs contain an intrinsically disordered region (IDR), which is commonly assumed to behave as a long, flexible polymeric tail composed of hundreds of amino acids. Recent experimental findings indicate that the IDR of certain TFs plays a pivotal role in the search process. However, the principles underlying the IDR’s role remain unclear. Here, we reveal key design principles of the IDR related to TF binding affinity and search time. Our results demonstrate that the IDR significantly enhances both of these aspects. Furthermore, our model shows good agreement with experimental results, and we propose further experiments to validate the model’s predictions.