Biomedical subjects

Ned S Wingreen

Publications and source records attributed to Ned S Wingreen.

5 recordsLinked to original sources

PubMed2026

Cell-body curvature reduces stall frequency to enhance Vibrio cholerae swimming and chemotaxis through hydrogels.

The swimming motility of the bacterial pathogen Vibrio cholerae is a virulence factor that aids in breaching the mucus layer. V. cholerae has a curved cell shape, and previous work demonstrated that loss of curvature decreases infectivity. Here, we investigate the mechanism by which curvature affects single-cell motility. We compared the chemotactic performance of wild-type curved cells and straight mutants. The two exhibit similar swimming properties in liquid and viscous solutions but differ significantly in mucus-mimicking hydrogels, where curved cells demonstrate an 86% increase in chemotactic drift. Trajectory analysis indicates comparable swimming speeds, but straight mutants experience more frequent stalls, reducing total swimming time. Stalls further reduce chemotactic performance by imposing an average reorientation down the chemical gradient, regardless of cell shape. Coarse-grained molecular dynamics simulations corroborate these results across intestinal mucus hydrogel stiffnesses and identify an optimal curvature for movement through hydrogel-like meshes, close to the pathogen's median curvature. These findings highlight cell shape's role in pathogenicity and the need to study bacterial behaviors under conditions more closely mimicking the host environment.

Vibrio cholerae↗

PubMed2026

The value of a prophage-borne defense system in phage-phage competition.

Temperate phages that incorporate into their bacterial hosts' genomes often encode defense systems that protect their hosts from superinfection by unrelated phages. Yet the evolutionary value of such defenses to the phage remains unclear. We present a minimal theoretical framework to quantify the selective advantage of a prophage-borne defense system in competition between temperate phages infecting the same bacterial host. The model reveals regimes in which a "defensive phage" can invade and persist despite growth costs, regimes of bistability, and others in which all phage types coexist due to a rock-paper-scissors-like dynamic between defensive, non-defensive, and defense-loss variants. Because defense systems can be non-transitive, true rock-paper-scissors relations can lead to persistent oscillations. These results identify simple conditions under which phage-encoded defense systems are evolutionarily stable, providing testable predictions for the prevalence and maintenance of these systems in natural microbial communities.

Prophages↗

PubMed2025

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.

Journal Article↗

PubMed2025

Analysis of gene expression within individual cells reveals spatiotemporal patterns underlying Vibrio cholerae biofilm development.

Bacteria commonly exist in multicellular, surface-attached communities called biofilms. Biofilms are central to ecology, medicine, and industry. The Vibrio cholerae pathogen forms biofilms from single founder cells that, via cell division, mature into three-dimensional structures with distinct, yet reproducible, regional architectures. To define mechanisms underlying biofilm developmental transitions, we establish a single-molecule fluorescence in situ hybridization (smFISH) approach that enables accurate quantitation of spatiotemporal gene-expression patterns in biofilms at cell-scale resolution. smFISH analyses of V. cholerae biofilm regulatory and structural genes demonstrate that, as biofilms mature, overall matrix gene expression decreases, and simultaneously, a pattern emerges in which matrix gene expression becomes largely confined to peripheral biofilm cells. Both quorum sensing and c-di-GMP-signaling are required to generate the proper temporal pattern of matrix gene expression. Quorum sensing signaling is uniform across the biofilm, and thus, c-di-GMP-signaling alone sets the regional matrix gene expression pattern. The smFISH strategy provides insight into mechanisms conferring particular fates to individual biofilm cells.

Biofilms↗

PubMed2022

Morphological instability and roughening of growing 3D bacterial colonies.

How do growing bacterial colonies get their shapes? While colony morphogenesis is well studied in two dimensions, many bacteria grow as large colonies in three-dimensional (3D) environments, such as gels and tissues in the body or subsurface soils and sediments. Here, we describe the morphodynamics of large colonies of bacteria growing in three dimensions. Using experiments in transparent 3D granular hydrogel matrices, we show that dense colonies of four different species of bacteria generically become morphologically unstable and roughen as they consume nutrients and grow beyond a critical size-eventually adopting a characteristic branched, broccoli-like morphology independent of variations in the cell type and environmental conditions. This behavior reflects a key difference between two-dimensional (2D) and 3D colonies; while a 2D colony may access the nutrients needed for growth from the third dimension, a 3D colony inevitably becomes nutrient limited in its interior, driving a transition to unstable growth at its surface. We elucidate the onset of the instability using linear stability analysis and numerical simulations of a continuum model that treats the colony as an "active fluid" whose dynamics are driven by nutrient-dependent cellular growth. We find that when all dimensions of the colony substantially exceed the nutrient penetration length, nutrient-limited growth drives a 3D morphological instability that recapitulates essential features of the experimental observations. Our work thus provides a framework to predict and control the organization of growing colonies-as well as other forms of growing active matter, such as tumors and engineered living materials-in 3D environments.

Models, Biological↗