Researcher profile

Ned S. Wingreen

Ned S. Wingreen contributes to research discovery and scholarly infrastructure.

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Published work

7 published item(s)

preprint2026arXiv

Propelling catalytic structures using active phase separation

Living systems routinely consume energy to achieve motility, often using intricate biomolecular machinery. In this work, we show that active droplets can sustain indefinite self-propulsion of a spherical colloid in an otherwise homogeneous, isotropic, and autonomous environment. Our proposed minimal mechanism consists of phase-separating proteins, enzymes passivating them, and complementary enzymes anchored to the colloid surface that reactivate the proteins. This passivation-activation cycle gives rise to a symmetry breaking - nucleation and stabilization of a condensate near the colloid surface, which in turn exerts a repulsive force on the colloid. We numerically demonstrate that this mechanism can propel micron-sized colloids at speeds of up to a hundred microns per second. This propulsion mode is strongly resistant to Brownian fluctuations and external forces, suggesting that propulsion mechanisms based on biomolecular condensates may offer a complementary, motor-free route to biological transport.

preprint2026arXiv

Roadmap for Condensates in Cell Biology

Biomolecular condensates govern essential cellular processes yet elude description by traditional equilibrium models. This roadmap, distilled from structured discussions at a workshop and reflecting the consensus of its participants, clarifies key concepts for researchers, funding bodies, and journals. After unifying terminology that often separates disciplines, we outline the core physics of condensate formation, review their biological roles, and identify outstanding challenges in nonequilibrium theory, multiscale simulation, and quantitative in-cell measurements. We close with a forward-looking outlook to guide coordinated efforts toward predictive, experimentally anchored understanding and control of biomolecular condensates.

preprint2025arXiv

Accelerated Ostwald ripening by chemical activity

Phase separation of biomolecular condensates promotes membrane-free compartmentalization in cells. The dynamics of these biocondensates is routinely regulated by energy-consuming processes. Here, we devise a theory pinpointing how active chemical reactions, interconverting molecules between phase-separating and inert forms, can drive faster condensate coarsening. We find that mass conservation limits droplet volume growth to being linear in time regardless of activity, resembling the passive Lifshitz-Slyozov law. However, if reactions are restricted to occur only outside droplets, the rate of Ostwald ripening can be increased by an arbitrarily large factor. Our theory is quantitatively supported by recent experiments on ripening in the presence of fueled interconversion reactions, under precisely the predicted conditions. We posit that the ability to induce rapid biocondensate coarsening can be advantageous in synthetic-biological contexts, e.g., as a regulator of metabolic channeling.

preprint2021arXiv

Stoichiometry controls the dynamics of liquid condensates of associative proteins

Multivalent associative proteins with strong complementary interactions play a crucial role in phase separation of intracellular liquid condensates. We study the internal dynamics of such "bond-network" condensates comprised of two complementary proteins via scaling analysis and molecular dynamics. We find that when stoichiometry is balanced, relaxation slows down dramatically due to a scarcity of alternative partners following a bond break. This microscopic slow-down strongly affects the bulk diffusivity, viscosity and mixing, which provides a means to experimentally test our predictions.

preprint2019arXiv

Magic numbers in polymer phase separation -- the importance of being rigid

Cells possess non-membrane-bound bodies, many of which are now understood as phase-separated condensates. One class of such condensates is composed of two polymer species, where each consists of repeated binding sites that interact in a one-to-one fashion with the binding sites of the other polymer. Previous biologically-motivated modeling of such a two-component system surprisingly revealed that phase separation is suppressed for certain combinations of numbers of binding sites. This phenomenon, dubbed the "magic-number effect", occurs if the two polymers can form fully-bonded small oligomers by virtue of the number of binding sites in one polymer being an integer multiple of the number of binding sites of the other. Here we use lattice-model simulations and analytical calculations to show that this magic-number effect can be greatly enhanced if one of the polymer species has a rigid shape that allows for multiple distinct bonding conformations. Moreover, if one species is rigid, the effect is robust over a much greater range of relative concentrations of the two species. Our findings advance our understanding of the fundamental physics of two-component polymer-based phase-separation and suggest implications for biological and synthetic systems.

preprint2019arXiv

Non-uniform growth and surface friction determine bacterial biofilm morphology on soft substrates

During development, organisms acquire three-dimensional shapes with important physiological consequences. While the basic mechanisms underlying morphogenesis are known in eukaryotes, it is often difficult to manipulate them in vivo. To circumvent this issue, here we present a study of developing Vibrio cholerae biofilms grown on agar substrates in which the spatiotemporal morphological patterns were altered by varying the agar concentration. Expanding biofilms are initially flat, but later experience a mechanical instability and become wrinkled. Whereas the peripheral region develops ordered radial stripes, the central region acquires a zigzag herringbone-like wrinkle pattern. Depending on the agar concentration, the wrinkles initially appear either in the peripheral region and propagate inward (low agar concentration) or in the central region and propagate outward (high agar concentration). To understand these experimental observations, we developed a model that considers diffusion of nutrients and their uptake by bacteria, bacterial growth/biofilm matrix production, mechanical deformation of both the biofilm and the agar, and the friction between them. Our model demonstrates that depletion of nutrients beneath the central region of the biofilm results in radially-dependent growth profiles, which in turn, produce anisotropic stresses that dictate the morphology of wrinkles. Furthermore, we predict that increasing surface friction (agar concentration) reduces stress anisotropy and shifts the location of the maximum compressive stress, where the wrinkling instability first occurs, toward the center of the biofilm, in agreement with our experimental observations. Our results are broadly applicable to bacterial biofilms with similar morphologies and also provide insight into how other bacterial biofilms form distinct wrinkle patterns.

preprint2018arXiv

Regulation of T cell expansion by antigen presentation dynamics

An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response to infection while avoiding immunopathology. Recent experiments in mice have demonstrated that the expansion of a specific clone of T cells in response to cognate antigen obeys a striking inverse power law with respect to the initial number of T cells. Here, we show that such a relationship arises naturally from a model in which T cell expansion is limited by decaying levels of presented antigen. The same model also accounts for the observed dependence of T cell expansion on affinity for antigen and on the kinetics of antigen administration. Extending the model to address expansion of multiple T cell clones competing for antigen, we find that higher affinity clones can suppress the proliferation of lower affinity clones, thereby promoting the specificity of the response. Employing the model to derive optimal vaccination protocols, we find that exponentially increasing antigen doses can achieve a nearly optimized response. We thus conclude that the dynamics of presented antigen is a key regulator of both the size and specificity of the adaptive immune response.