Physical Review Letters

The mechanical properties of cytoplasm are crucial for cellular functions. While active processes significantly alter cytoplasmic viscoelasticity, the physical mechanisms remain elusive. Here, we model the cytoplasm as a colloidal suspension subject to passive and active noise, coarse-grained as an effective temperature. We show that a jammed cytoplasm transitions from a solid to a liquid phase at a critical effective temperature. Intriguingly, the simulated complex shear modulus at the critical state exhibits a 1/2 power-law scaling with frequency and quantitatively matches the experimental data of live cells without fitting parameters, given that the cytoplasmic volume fraction is slightly above the jamming transition. We further reveal the biological significance for the cytoplasm to be slightly above jamming: it is a regime in which the viscosity is ultrasensitive to changes in the effective temperature. Our results suggest that cells actively regulate their volume fractions in the sensitive regime in which they can tune cytoplasmic viscosity efficiently via active processes.

The holonomic brain theory--originally formulated to account for the need of non-local memory encoding in cognitive systems--could gain new theoretical traction when integrated with holographic principles from physics, most notably the AdS/CFT correspondence. Recent findings in neuroscience suggest that conformal field theories (CFTs), emerging at critical points across spatiotem-poral scales in neural dynamics, are essential for brain function. Concurrently, black-brane geometries, long studied in gravitational physics, can find unexpected analogues in the interplay of active matter dynamics and the brains neuroanatomical organization. Motivated by these parallels, we posit a generalized holographic framework and interrogate its validity through the fluid/gravity duality--a correspondence linking hydrodynamic equations to gravitational spacetime metrics. In this work, we explore the holographic principles at the Navier-Stokes regime, demonstrating that holography can model key neurophysiological mechanisms: cerebral autoregulation (the brains hemodynamic self-stabilization) and neurovascular coupling (the dynamic neuron-bloodflow interplay). This work bridges holography, active matter physics, and neuroscience, proposing a unified framework to decode the brains multiscale organization, its resilience to perturbations, and its computational capabilities. By grounding neurovascular physiology in gravitational duals, we open pathways to reinterpret brain function through the lens of emergent spacetime geometry.

We study how simple eukaryotic organisms make decisions in response to competing stimuli in the context of phototaxis by the unicellular alga Chlamydomonas reinhardtii. While negatively phototactic cells swim directly away from a collimated light beam, when presented with two beams of adjustable intersection angle and intensities, we find that cells swim in a direction given by an intensity-weighted average of the two light propagation vectors. This geometrical law is a fixed point of an adaptive model of phototaxis and minimizes the average light intensity falling on the anterior pole of the cell. At large angular separations, subpopulations of cells swim away from one source or the other, or along the direction of the geometrical law, with some cells stochastically switching between the three directions. This behavior is shown to arise from a population-level distribution of photoreceptor locations that breaks front-back symmetry of photoreception.

Exocytosis plays a crucial role in regulating the growth and migration of filamentous tip-growing cells. We present a mathematical framework that infers the spatial profile of exocytosis from the cell morphology in self-similar growing cells that elongate while preserving their apical domain shapes. By applying the framework to cell wall outline data from experiments across walled cell species, we find that while tapered cells have their exocytosis concentrated at the apex, cells with flatter tip shape beyond a threshold require exocytosis to peak in an annulus region away from the apex.

Biomolecular condensates frequently rely on membrane interactions for recruitment, localization, and biochemical substrates. Many of these interactions are mediated by membrane-anchored molecules such as proteins or specific lipids, which we refer to as "mobile tethers" since they can typically diffuse within the membrane while still interacting with the condensate. The presence of mobile tethers creates a surface with dynamic and spatially inhomogeneous wetting properties that are typically overlooked by traditional wetting theories. Here, we propose a general theoretical framework to study how mobile tethers impact both equilibrium and dynamic properties of condensate wetting. We show that a favorable tether-condensate interaction leads to tether enrichment at the condensate-membrane interface, which modifies the equilibrium surface tension and contact angle. Increasing tether abundance on the membrane can drive transitions between wetting regimes, with only a modest tether density and binding energy required for biologically relevant scenarios. Furthermore, tethers modulate how condensates react to complex membrane geometries. By helping condensates coat membranes, mobile tethers can facilitate condensate localization to junctions of membrane structures, such as the reticulated membranes inside the algal pyrenoid. Both tether abundance and mobility affect how droplets interact with complex membrane geometries, such as droplet migration along membrane tubules of varying radii. These results provide a framework to study the implications of tether-mediated condensate-membrane interactions for cellular organization and function.

Hydrodynamic coordination of cilia is ubiquitous in biology. It is commonly modeled using the steady Stokes equations. The flow around ciliated cells, however, exhibits finite time vorticity diffusion, requiring a dynamical description. We present a model of elastic cilia coupled by transient viscous flow in the bulk fluid. Therein, vorticity diffusion impacts cilia coordination qualitatively and quantitatively. In particular, pairs of cilia synchronize in antiphase for long diffusion times. Moreover, metachronal waves occur in cilia chains larger than the viscous penetration depth, whereas global synchronization occurs in Stokes flow.

Self-organization of cells into higher-order structures is key for multicellular organisms, e.g. during embryonic epithelium formation via repetitive replication of template-like founder cells. Yet, very similar spatial arrangements of cell-like compartments (protocells) are also seen in cell extracts in the absence of template structures and genetic material. Here we show that protocell patterns are highly organized, featuring a spatial arrangement and coarsening like two-dimensional foams but without signatures of disordered hyperuniformity. These features even remain unaffected when enforcing smaller protocells by stabilizing microtubule filaments. Comparing our data to generic models, we conclude that protocell patterns emerge by simultanous formation of randomly placed seeds that grow at a uniform rate until fusion of adjacent protocells drives coarsening. The strong similarity of our observations to the recently reported organization of epithelial monolayers suggests common generic principles for space allocation in living matter.

Material renewability in active living systems, such as in cells and tissues, can drive the large-scale patterning of forces, with distinctive phenotypic consequences. This is especially significant in the cell cytoskeleton, where multiple species of myosin bound to actin, apply differential contractile stresses and undergo differential turnover, giving rise to patterned force channeling. Here we study the dynamical patterning of stresses that emerge in a hydrodynamic description of a renewable active actomyosin elastomer comprising two myosin species. Our analytical framework also holds for an actomyosin elastomer with a single myosin species. We find that a uniform active contractile elastomer spontaneously segregates into spinodal stress patterns, followed by a finite-time collapse into tension carrying singular structures that display self-similar scaling and caustics. Our numerical analysis carried out in 1D, shows that these singular structures move and merge, and gradually result in a slow coarsening dynamics. We discuss the implications of our findings to the emergence of stress fibers and the spatial patterning of actomyosin. Our study suggests, that with state-dependent turnover of crosslinkers and myosin, the in vivo cytoskeleton can navigate through the space of material parameters to achieve a variety of functional phenotypes.

Biased locomotion is a common feature of microorganisms, but little is known about its impact on self-organisation. Inspired by recent experiments showing a transition to large-scale flows, we study theoretically the dynamics of magnetotactic bacteria confined to a drop. We reveal two symmetry-breaking mechanisms (one local chiral and one global achiral) leading to self-organisation into global vortices and a net torque exerted on the drop. The collective behaviour is ultimately controlled by the swimmers microscopic chirality and, strikingly, the system can exhibit oscillations and memory-like features.

In a recent proposal on the experimental tests of quantum gravity creation of non-Gaussianity in a Bose-Einstein condensate (BEC) has been suggested as a decisive confirmation of quantum gravity. In a related proposal, a gas of ultracold Rb or Cs atoms has previously been suggested as a possible platform for tests of quantum gravity. Since a practical demonstration of above proposals is a very challenging and costly affair, exploring cost-effective alternatives to these technologically demanding experimental protocols becomes very important. We here show that the phenomenon of Bicoid (Bcd) gradient formation in the early fruit fly embryo, considered basically here as a multipartite quantum system with an ensemble of initial states and a unitary evolution U that implements a quantum Newtonian Hamiltonian over this gravitationally interacting system, naturally combines the essential features of above proposals in a single system giving a viable signature of quantum gravity through the creation of non-Gaussianity. We conclude that although the phenomenon of Bcd gradient formation in the early Drosophila embryo is accompanied by quantum gravitational effects, it might need further experiments to verify such a noval claim.

Biomolecular condensates are viscoelastic, and their mechanical properties are intimately related to their biological functions. However, the connection between microscopic networks formed by intermolecular crosslinks and viscoelasticity is still elusive. Here, we model biomolecular condensates as random crosslinked polymer solutions to elucidate how random connectivity fundamentally alters their viscoelasticity. We decompose the entire solution into multiple tree networks and demonstrate that for networks with size n, their spectra of relaxation rates{lambda} exhibit a power-law scaling pn({lambda}) [~]{lambda} -1/3 with a lower cutoff{lambda} min [~] n-3/2. By integrating all networks, we show that for the entire solution, random crosslinks generate an abundance of soft modes involving multiple linear polymers with a flat spectrum of relaxation rates. The soft modes cause anomalous linear frequency scaling of the dynamic modulus, in particular, they significantly boost the low-frequency storage modulus relative to uncrosslinked systems. Our predictions agree quantitatively with the experimental data from distinct biomolecular condensates.

Recent work on distinct multicellular organisms has revealed a hitherto unknown type of biological noise; rather than a regular arrangement, cellular neighborhood volumes, obtained by Voronoi tessellations of the cell locations, are broadly distributed and consistent with gamma distributions. We propose an explanation for those observations in the case of the alga Volvox, whose somatic cells are embedded in an extracellular matrix (ECM) they export. Both a solvable one-dimensional model of ECM growth derived from bursty transcriptional activity and a two-dimensional "Voronoi liquid" model are shown to provide one-parameter families that smoothly interpolate between the empirically-observed near-maximum-entropy gamma distributions and the crystalline limit of Gaussian distributions governed by the central limit theorem. These results highlight a universal consequence of intrinsic biological noise on the architecture of certain tissues.

Within a living cell, the myriad of proteins that bind DNA introduce heterogeneously spaced kinks into an otherwise semiflexible DNA double helix. To investigate the effects of heterogeneous nucleosome binding on chromatin organization, we extend the wormlike chain (WLC) model to include statistically spaced, rigid kinks. On time scales where nucleosome positions are fixed, we find that the probability of chromatin loop formation can differ by up to six orders of magnitude between two sets of nucleosome positions drawn from the same distribution. On longer time scales, we show that continuous re-randomization due to nucleosome turnover results in chromatin tracing out an effective WLC with a dramatically smaller Kuhn length than bare DNA. Together, these observations demonstrate that heterogeneity in nucleosome spacing acts as the dominant source of chromatin elasticity and governs both local and global chromatin organization.

Muscle is a complex hierarchically organized soft contractile engine. To understand the limits on the rate of contraction and muscle energetics, we construct a coarse-grained multiscale model that integrates over molecular details and describes muscle as an active sponge. Our analysis of existing experiments highlights the importance of spatially heterogeneous strains and local volumetric deformations in muscular contractions across species and muscle type. The minimal theoretical model shows how contractions generically induce intracellular fluid flow and power active hydraulic oscillations, which determine the limits of ultrafast muscular contractions. We further demonstrate that the viscoelastic response of muscle is naturally nonreciprocal - or odd - owing to its active and anisotropic nature. This points to an alternate mode of muscular power generation from periodic cycles in spatial strain alone, contrasting with previous descriptions based on temporal cycles. Our work suggests the need for a revised view of muscle dynamics that emphasizes the multiscale spatio-temporal origins of soft hydraulic power, with potential implications for physiology, biomechanics and locomotion.

We present a novel mean-field theory for balanced neuronal networks with arbitrary levels of symmetry in the synaptic connectivity. The theory determines the fixed point of the network dynamics and the conditions for its stability. The fixed point becomes unstable by increasing the synaptic gain beyond a critical value that depends on the level of symmetry. Beyond this critical gain, for positive levels of symmetry, we find a previously unreported phase. In this phase, the dynamical landscape is dominated by a large number of marginally-stable fixed points. As a result, the network dynamics exhibit non-exponential relaxation and ergodicity is broken. We discuss the relevance of such a glassy phase for understanding dynamical and computational aspects of cortical operation.

In order to proliferate, bacteria must remodel their cell wall at the division site. The division process is driven by the enzymatic activity of peptidoglycan (PG) synthases and hydrolases around the constricting Z-ring. PG remodelling is reg-ulated by de-and re-crosslinking enzymes, and the directing constrictive force of the Z-ring. We introduce a model that is able to reproduce correctly the shape of the division site during the constriction and septation phase of E. coli. The model represents mechanochemical coupling within the mathematical framework of morphoelasticity. It contains only two parameters, associated with volumet-ric growth and PG remodelling, that are coupled to the mechanical stress in the bacterial wall. Different morphologies, corresponding either to mutant or wild type cells were recovered as a function of the remodeling parameter. In addition, a plausible range for the cell stiffness and turgor pressure was determined by comparing numerical simulations with bacterial cell lysis data.

Fluid-filled biological cavities are ubiquitous, but their collective dynamics has remained largely unexplored from a physical perspective. Based on experimental observations in early embryos, we propose a model where a cavity forms through the coarsening of myriad of pressurized micrometric lumens, that interact by ion and fluid exchanges through the intercellular space. Performing extensive numerical simulations, we find that hydraulic fluxes lead to a self-similar coarsening of lumens in time, characterized by a robust dynamic scaling exponent. The collective dynamics is primarily controlled by hydraulic fluxes, which stem from lumen pressures differences and are dampened by water permeation through the membrane. Passive osmotic heterogeneities play, on the contrary, a minor role on cavity formation but active ion pumping can largely modify the coarsening dynamics: it prevents the lumen network from a collective collapse and gives rise to a novel coalescence-dominated regime exhibiting a distinct scaling law. Interestingly, we prove numerically that spatially biasing ion pumping may be sufficient to position the cavity, suggesting a novel mode of symmetry breaking to control tissue patterning. Providing generic testable predictions, our model forms a comprehensive theoretical basis for hydro-osmotic interaction between biological cavities, that shall find wide applications in embryo and tissue morphogenesis. Author summaryThe formation of a single biological cavity, or lumen, in tissues and embryos has been widely studied experimentally but the collective dynamics of multiple lumens has received much less attention. Here, we focus on a particular type of lumens, which are located at the adhesive side of cells and can therefore interact directly through the intercellular space, as recently observed in the very first stages of embryogenesis. We propose a generic model to describe the hydraulic and osmotic exchanges between lumens themselves, and with the surrounding cellular medium. Lumens are pressurized by a surface tension, which leads naturally to their coarsening into a single final cavity through hydraulic exchanges. With extensive numerical simulations and mean-field theory we predict that such coarsening dynamics follows a robust scaling law, that barely depends on concentration heterogeneities between lumens. On the contrary, active osmotic pumping largely influences the collective dynamics by favoring lumen coalescence and by biasing the position of the final cavity. Our theoretical work highlights the essential role of hydraulic and osmotic flows in morphogenesis.

We contradict diverse mathematical claims of a paper by Casey O. Barkan and Robijn F. Bruinsma in PNAS 2024, 121, No. 6, e2315866121, former BioRxiv preprint from Sept.12,2023. It deals with the physical mechanisms of protein-ligand catch bonding for the family of selectin proteins. Selectins exhibit slip, catch-slip, and slip-catch-slip bonding.

Non-compact symmetries such as SU(1,1) govern quantum amplification and squeezing, yet have not been directly identified in macroscopic spin ensembles. Here we apply a symmetry-based analytical framework to previously published magnetic resonance data acquired from proton spin ensembles in the living human brain. By reanalyzing the zero-quantum (ZQ) signal within this framework, we isolate a non-compact SU(1,1) sector of the full SU(4) spin algebra and exclude all compact SU(2) exchange pathways. A calibrated signal-level witness links the measured ZQ amplitude to the off-diagonal density-matrix element, yielding a direct lower bound on concurrence. The observed signal exceeds the separability threshold, confirming bipartite entanglement within the SU(1,1) manifold. This non-compact symmetry defines a hyperbolic temporal geometry that can be interpreted holographically as a non-traversable wormhole connecting correlated spin sectors. Such an entangled bridge provides a natural physical analogue of working memory. Independent evidence shows that the same magnetic-resonance signal correlates with short-term memory performance, supporting this interpretation and suggesting that transient SU(1,1) entanglement in the brains proton spin ensemble may underlie a functional holographic memory mechanism.

We develop a surrogate model for low complexity disordered proteins, which allows us to generate sequences with quantifiable disorder. We investigate properties of these sequences, and show that the sequence dependence of the radius of gyration only arises in the vicinity of the polymer collapse transition. Microphase propensity of the sequence is shown to be a reliable predictor, outperforming state of the art methods, in the crossover region. We show that predictions of associative polymer theory arises only as a limiting case, and discuss its applicability.