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            Information is an important resource. Storing and retrieving information faithfully are huge challenges and many methods have been developed to understand the principles behind robust information processing. In this review, we focus on information storage and retrieval from the perspective of energetics, dynamics, and statistical mechanics. We first review the Hopfield model of associative memory, the classic energy-based model of memory. We then discuss generalizations and physical realizations of the Hopfield model. Finally, we highlight connections to energy-based neural networks used in deep learning. We hope this review inspires new directions along the lines of information storage and retrieval in physical systems.more » « lessFree, publicly-accessible full text available April 21, 2026
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            Pooled single-cell perturbation screens represent powerful experimental platforms for functional genomics, yet interpreting these rich datasets for meaningful biological conclusions remains challenging. Most current methods fall at one of two extremes: either opaque deep learning models that obscure biological meaning, or simplified frameworks that treat genes as isolated units. As such, these approaches overlook a crucial insight: gene co-fluctuations in unperturbed cellular states can be harnessed to model perturbation responses. Here we present CIPHER (Covariance Inference for Perturbation and High-dimensional Expression Response), a framework leveraging linear response theory from statistical physics to predict transcriptome-wide perturbation outcomes using gene co-fluctuations in unperturbed cells. We validated CIPHER on synthetic regulatory networks before applying it to 11 large-scale single-cell perturbation datasets covering 4,234 perturbations and over 1.36M cells. CIPHER robustly recapitulated genome-wide responses to single and double perturbations by exploiting baseline gene covariance structure. Importantly, eliminating gene-gene covariances, while retaining gene-intrinsic variances, reduced model performance by 11-fold, demonstrating the rich information stored within baseline fluctuation structures. Moreover, gene-gene correlations transferred successfully across independent experiments of the same cell type, revealing stereotypic fluctuation structures. Furthermore, CIPHER outperformed conventional differential expression metrics in identifying true perturbations while providing uncertainty-aware effect size estimates through Bayesian inference. Finally, most genome-wide responses propagated through the covariance matrix along approximately three independent and global gene modules. CIPHER underscores the importance of theoretically-grounded models in capturing complex biological responses, highlighting fundamental design principles encoded in cellular fluctuation patterns.more » « lessFree, publicly-accessible full text available July 1, 2026
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            Nonreciprocal interactions fueled by local energy consumption can be found in biological and synthetic active matter at scales where viscoelastic forces are important. Such systems can be described by “odd” viscoelasticity, which assumes fewer material symmetries than traditional theories. Here we study odd viscoelasticity analytically and using lattice Boltzmann simulations. We identify a pattern-forming instability which produces an oscillating array of fluid vortices, and we elucidate which features govern the growth rate, wavelength, and saturation of the vortices. Our observation of pattern formation through odd mechanical response can inform models of biological patterning and guide engineering of odd dynamics in soft active matter systems. Published by the American Physical Society2024more » « less
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            We consider an immersed elastic body that is actively driven through a structured fluid by a motor or an external force. The behavior of such a system generally cannot be solved analytically, necessitating the use of numerical methods. However, current numerical methods omit important details of the microscopic structure and dynamics of the fluid, which can modulate the magnitudes and directions of viscoelastic restoring forces. To address this issue, we develop a simulation platform for modeling viscoelastic media with tensorial elasticity. We build on the lattice Boltzmann algorithm and incorporate viscoelastic forces, elastic immersed objects, a microscopic orientation field, and coupling between viscoelasticity and the orientation field. We demonstrate our method by characterizing how the viscoelastic restoring force on a driven immersed object depends on various key parameters as well as the tensorial character of the elastic response. We find that the restoring force depends non-monotonically on the rate of diffusion of the stress and the size of the object. We further show how the restoring force depends on the relative orientation of the microscopic structure and the pulling direction. These results imply that accounting for previously neglected physical features, such as stress diffusion and the microscopic orientation field, can improve the realism of viscoelastic simulations. We discuss possible applications and extensions to the method.more » « less
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            In nature, several ciliated protists possess the remarkable ability to execute ultrafast motions using protein assemblies called myonemes, which contract in response to Ca 2+ ions. Existing theories, such as actomyosin contractility and macroscopic biomechanical latches, do not adequately describe these systems, necessitating development of models to understand their mechanisms. In this study, we image and quantitatively analyze the contractile kinematics observed in two ciliated protists ( Vorticella sp. and Spirostomum sp.), and, based on the mechanochemistry of these organisms, we propose a minimal mathematical model that reproduces our observations as well as those published previously. Analyzing the model reveals three distinct dynamic regimes, differentiated by the rate of chemical driving and the importance of inertia. We characterize their unique scaling behaviors and kinematic signatures. Besides providing insights into Ca 2+ -powered myoneme contraction in protists, our work may also inform the rational design of ultrafast bioengineered systems such as active synthetic cells.more » « less
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