Phosphatidylcholine liposomes fill a special niche in alleviating osteoarthritis via intra-articular (IA) administration, attributed to their superlubricity at the articular cartilage surface, but their co-utilization as drug delivery vesicles in such therapy remains challenging as they may rupture under mechanical stress. Here, we describe cytoskeleton-inspired, supramolecular, self-assembled nanolipogels (NLGs), encompassing liposome-encased nanogels with a dynamic network formed by hydrogen bonding and cation-pi interactions, as a platform for simultaneous robust drug-delivery and massive reduction of interfacial frictional dissipation. We use a surface force balance to assess such dissipation at the sub-nanometer level, elucidating the mechanism involved, and atomic force microscopy to probe the NLGs structural stability. A useful proxy for the interfacial dissipation is the coefficient of friction, which remains as low as 10-4 at contact pressures at least up to 2 MPa, while under higher pressures exceeding the H-bonding energy density it increases abruptly and irreversibly to the still-low value 10-2. Under sustained sliding above this threshold, however, friction gradually decreases again, indicating recovery of the lubricating interface. Molecular dynamics simulations identify the compressive stress decrease due to hydrogen-bond rupture/rearrangement within the nanogel as a buried supramolecular transition associated with lubrication breakdown and recovery, while cargo release during sliding emphasizes the drug-delivery potential of such NLGs. These findings reveal how supramolecular core-shell reinforcement regulates load-bearing hydration lubrication, and provides a framework for designing adaptive biomimetic lubricants which are at the same time load-bearing intra-articular cargo-delivery vehicles.

Modern microscopy systems integrate heterogeneous hardware devices that require dedicated software for coordination. However, high-performance C++ implementations of microscopy control software remain scarce. We present ScopeOne, a C++ and Qt-based microscopy control software built on the MicroManager hardware abstraction layer. Through process isolation and shared memory, ScopeOne achieves simultaneous multi-camera preview with real-time image processing, while maintaining full compatibility with the μManager device ecosystem.

Modeling the circadian impact of seasonal clock changing requires precise synchronization between solar and social time. This report critiques a recent study that associated disease prevalence in the United States with seasonal clock exposure. We identify a fundamental computational error in which a sign reversal of the longitudinal offset effectively inverted the US East-West axis, cross-correlating local health data with the circadian burden of hypothetical locations on the opposite side of a time zone. We outline the methodology for a correct modelization of the circadian process in the context of US geography.

In the last years, an anomalously high spreading of West Nile virus (WNV) has been observed in Italy, with particularly high peaks of infections in southern Lazio, Campania and Veneto regions. The main disease vector for WNV is represented by Culex pipiens mosquitoes, which spread human infections through their bites. Here, we investigate WNV fever epidemic diffusion during summer season 2025 in Italy through a computational approach based on a quantum version of the Game of Life (GOL) cellular automaton model. Specifically, human dynamics evolves according to the GOL rules, while stochastic dynamics of disease vectors, i.e., mosquitoes, as well as their interaction with humans, simultaneously occur. We show that this model fits the curves of cumulative infected individuals with high accuracy, either at local and average-regional level, with only optimization of mosquito birth and removal rates parameters. Furthermore, leveraging model flexibility, we show that changes in model parameters values elucidate system response to environmental variations. For instance, we quantify, e.g., the impact of mosquito spreading containment measures or sudden mosquito increasing abundance due to climatic and ecological changes. Overall, we provide a general, quantitative description of WNV infection spreading in Italy which could represent a supportive tool to test different environmental scenarios and could be useful to devise strategies for decision makers to monitor disease vector dynamics and to control consequent virus diffusion.

We introduce a shape-based polar order parameter that captures the structural asymmetry of cells within epithelial monolayers. By combining bright-field imaging and traction force microscopy, we demonstrate that shape polarity serves as a unifying biomechanical metric, integrating the physical information encoded by nematic directors, principal stresses, and cellular motion. Furthermore, we show that the tissue organizes into a mixed polar-nematic phase, characterized by the coexistence of integer ($\pm 1$) and half-integer ($\pm 1/2$) defects. Through mechanical perturbations, we demonstrate that both substrate stiffness and cell-cell adhesion modulate the density of these excitations and the length of domain walls binding like-signed positive half-integer defects. Using a minimal continuum model of polar-nematic active matter, we establish that this mixed phase is fundamentally driven by the interplay of active stresses and polar-nematic elasticity. These findings provide a direct experimental evidence that epithelial monolayers behave as nematopolar matter, in which coupled polar and nematic elastic interactions jointly shape the active state

Cellular signal processing performs reliably despite molecular noise. Mutual information (MI) is widely used to quantify signaling fidelity, capturing how well outputs discriminate input states. However, it fails to capture whether the output preserves the statistical structure of the input, a property crucial in morphogen patterning and dose-dependent signaling. To address this gap, we introduce the 2-Wasserstein (2-WD) distance, which provides a geometric basis for comparing input and output distributions. We define MI as informational fidelity (INF) and the inverse of the 2-WD as geometric fidelity (GMF). Applying this dual-fidelity framework to canonical regulatory motifs under Gaussian channel approximation reveals topology-dependent trade-offs: coherent feed-forward loops can perform well in both dimensions, whereas feedback architectures sacrifice INF to enhance GMF. Experimental analysis of tumor necrosis factor signaling supports the predicted role of feedback regulation. Analysis of RAS-MAPK signaling shows that intracellular signal relay is better described by a balance between INF and GMF than by information transmission alone. Our results demonstrate that reliable signaling need not maximize information alone, but can arise from balancing information transmission with distributional correspondence. Thus, GMF represents a distinct dimension of signaling fidelity and provides a framework for analyzing natural networks and designing task-specific synthetic circuits.

Liquid mixtures can separate into phases with distinct composition. This phenomenon has recently come back to prominence due to its role in complex biological liquids, such as the cytoplasm, which contain thousands of components. For simple two-component mixtures phase-separated states are global free energy minima. However, local free energy minima, i.e. metastable states, are known to play a dominant role in complex systems with many components. For example, Hopfield neural networks can retrieve information from partial cues via relaxation to metastable states. Under what conditions can phase separated states be metastable, and what are the implications for information processing in multicomponent liquids? In this work we develop the general thermodynamic formalism of metastable phase separation. We then apply this formalism to an illustrative toy example inspired by recent experiments, binary mixtures with high-order interactions. Finally, as core application of the formalism, we study metastability in Hopfield liquids, a class of multicomponent mixtures capable of storing information on the composition of phases. We show that these phases can be retrieved from partial cues via metastable phase separation. Spatial simulations of liquids with a large number of components match our analytical solution. Our work suggests that complex biological mixtures can perform information retrieval through metastable phase separation.

Human bone marrow stromal cells (BMSC) include skeletal stem cells with ground-breaking therapeutic potential. However, BMSC colonies have very heterogeneous in vivo behaviour, due to their different potency; this unpredictability is the greatest hurdle to the development of skeletal regeneration therapies. Colony-level heterogeneity urges a fundamental question: how is it possible that one colony as a collective unit behaves differently from another one? If cell-to-cell variability were just an uncorrelated random process, a million cells in a transplant-bound colony would be enough to yield statistical homogeneity, hence washing out any colony-level traits. A possible answer is that the differences between two originating cells are transmitted to their progenies and collectively persist through an hereditary mechanism. But non-genetic inheritance remains an elusive notion, both at the experimental and at the theoretical level. Here, we prove that heterogeneity in the lineage topology of BMSC clonal colonies is determined by heritable traits that regulate cell-cycle exit. The cornerstone of this result is the definition of a novel entropy of the colony, which measures the hereditary ramifications in the distribution of inactive cells across different branches of the proliferation tree. We measure the entropy in 32 clonal colonies, obtained from single-cell lineage tracing experiments, and show that in the greatest majority of clones this entropy is decisively smaller than that of the corresponding non-hereditary lineage. This result indicates that hereditary epigenetic factors play a major role in determining cycle exit of bone marrow stromal cells.

Living organisms rely on molecular networks, such as gene circuits and signaling pathways, for information processing and robust decision-making in crowded, noisy environments. Recent advances show that interacting biomolecules self-organize by phase transitions into coexisting spatial compartments called condensates, often on cellular surfaces such as chromatin and membranes. In this paper, we demonstrate that multicomponent fluids can be designed to recruit distinct condensates to surfaces with differing compositions, performing a form of surface classification by condensation. We draw an analogy to multidimensional classification in machine learning and explore how hidden species, analogous to hidden nodes, expand the expressivity and capacity of these interacting ensembles to facilitate complex decision boundaries. By simply changing levels of individual species, we find that the same molecular repertoire can be reprogrammed to solve new tasks. Together, our findings suggest that the physical processes underlying biomolecular condensates can encode and drive adaptive information processing beyond compartmentalization.

This paper considers systems in which two or more ligands bind independently to a common scaffold. Such systems arise in a range of applications, including immunotherapy and synthetic biology. We show that each stoichiometric compatibility class contains a unique steady state, and that this steady state is asymptotically stable. The main result gives a rigorous proof that the steady-state concentration of the fully bound complex, viewed as a function of the total scaffold concentration, has a unique maximum. This biphasic dose response is a characteristic feature of scaffolding systems and, in the special case of two ligands, plays an important role in the design and analysis of bispecific antibody drugs.

Soft and active condensed matter represent a class of fascinating materials that we encounter in our everyday lives -- and constitute life itself. Control signals interact with the dynamics of these systems, and this influence is formalized in control theory and optimal control. Recent advances have employed various control-theoretical methods to design desired dynamics, properties, and functionality. Here we provide an introduction to optimal control aimed at physicists working with soft and active matter. We describe two main categories of control, feedforward control and feedback control, and their corresponding optimal control methods. We emphasize their parallels to Lagrangian and Hamiltonian mechanics, and provide a worked example problem. Finally, we review recent studies of control in soft, active, and related systems. Applying control theory to soft, active, and living systems will lead to an improved understanding of the signal processing, information flows, and actuation that underlie the physics of life.

We report the experimental super-resolution of pairs of point-like fluorescent sources using a modified image inversion interferometer microscope. The technique is inspired by recent developments in the application of quantum parameter estimation theory to semiclassical imaging problems. We find that the image inversion technique requires special polarization filtering to account for the dipolar nature of the emission. Using an azimuthal polarizer, we obtain improvements in the Fisher information of point-source separation by over an order of magnitude relative to direct imaging. Unlike established super-resolution fluorescence techniques, the method does not require sequential photoswitching/blinking of the fluorophores, and thus could facilitate significant speed-ups for certain biological imaging/tracking tasks.