Dynamics of polymers in coarse-grained nematic solvents.

Polymers are a primary building block in many biomaterials, often interacting with anisotropic backgrounds. While previous studies have considered polymer dynamics within nematic solvents, rarely are the effects of anisotropic viscosity and polymer elongation differentiated. Here, we study polymers embedded in nematic liquid crystals with isotropic viscosity numerical simulations to explicitly investigate the effect of nematicity on macromolecular conformation and how conformation alone can produce anisotropic dynamics.

Borromean hypergraph formation in dense random rectangles.

We develop a minimal model to study the stochastic formation of Borromean links within topologically entangled networks without requiring the use of knot invariants. Borromean linkages may form in entangled solutions of open polymer chains or in Olympic gel systems such as kinetoplast DNA, but it is challenging to investigate this due to the difficulty of computing three-body link invariants. Here, we investigate rectangles randomly oriented in three Cartesian planes and densely packed within a volume, and evaluate them for Hopf linking and Borromean link formation.

Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen.

Toxin-antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR-NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides.

Chirality effects in molecular chainmail.

Motivated by the observation of positive Gaussian curvature in kinetoplast DNA networks, we consider the effect of linking chirality in square lattice molecular chainmail networks using Langevin dynamics simulations and constrained gradient optimization. Linking chirality here refers to ordering of over-under versus under-over linkages between a loop and its neighbors. We consider fully alternating linking, maximally non-alternating, and partially non-alternating linking chiralities.

A genetically encoded biosensor to monitor dynamic changes of c-di-GMP with high temporal resolution.

Monitoring changes of signaling molecules and metabolites with high temporal resolution is key to understanding dynamic biological systems. Here, we use directed evolution to develop a genetically encoded ratiometric biosensor for c-di-GMP, a ubiquitous bacterial second messenger regulating important biological processes like motility, surface attachment, virulence and persistence. The resulting biosensor, cdGreen2, faithfully tracks c-di-GMP in single cells and with high temporal resolution over extended imaging times, making it possible to resolve regulatory networks driving bimodal developmental programs in different bacterial model organisms.

Single-molecule analysis of solvent-responsive mechanically interlocked ring polymers and the effects of nanoconfinement from coarse-grained simulations.

In this study, we simulate mechanically interlocked semiflexible ring polymers inspired by the minicircles of kinetoplast DNA (kDNA) networks. Using coarse-grained molecular dynamics simulations, we investigate the impact of molecular topological linkage and nanoconfinement on the conformational properties of two- and three-ring polymer systems in varying solvent qualities. Under good-quality solvents, for two-ring systems, a higher number of crossing points lead to a more internally constrained structure, reducing their mean radius of gyration.

A Synthetic Cumate-Inducible Promoter for Graded and Homogenous Gene Expression in Pseudomonas aeruginosa.

Inducible gene expression systems are powerful genetic tools to study bacterial physiology, probing essential and toxic gene functions, gene dosage effects, and overexpression phenotypes. For the opportunistic human pathogen Pseudomonas aeruginosa, dedicated inducible gene expression systems are scarce. In the current study, we developed a minimal synthetic 4-isopropylbenzoic acid (cumate)-inducible promoter, called P, that is tunable over several orders of magnitude.

Percolation and dissolution of Borromean networks.

Inspired by experiments on topologically linked DNA networks, we consider the connectivity of Borromean networks, in which no two rings share a pairwise-link, but groups of three rings form inseparable triplets. Specifically, we focus on square lattices at which each node is embedded a loop which forms a Borromean link with pairs of its nearest neighbors. By mapping the Borromean link network onto a lattice representation, we investigate the percolation threshold of these networks (the fraction of occupied nodes required for a giant component), as well as the dissolution properties: the spectrum of topological links that would be released if the network were dissolved to varying degrees.

Nanopore translocation of topologically linked DNA catenanes.

The electrical signal associated with a biopolymer translocating through a nanoscale pore depends on the size, topology, and configuration of each molecule. Building upon recent interest in using solid-state nanopores for studying the topology of knotted and supercoiled DNA, we present experimental observations of topologically linked catenanes translocating through a solid-state nanopore. Using restriction enzymes, linked circular molecules were isolated from the mitochondrial DNA of Crithidia fasciculata, a structure known as a kinetoplast that comprises thousands of topologically interlocked minicircles.

Flatness and intrinsic curvature of linked-ring membranes.

Recent experiments have elucidated the physical properties of kinetoplasts, which are chain-mail-like structures found in the mitochondria of trypanosome parasites formed from catenated DNA rings. Inspired by these studies, we use Monte Carlo simulations to examine the behavior of two-dimensional networks ("membranes") of linked rings. For simplicity, we consider only identical rings that are circular and rigid and that form networks with a regular linking structure.

Trapping in self-avoiding walks with nearest-neighbor attraction.

The statistics of self-avoiding random walks have been used to model polymer physics for decades. A self-avoiding walk that grows one step at a time on a lattice will eventually trap itself, which occurs after an average of 71 steps on a square lattice. Here, we consider the effect of nearest-neighbor attractive interactions on isolated growing self-avoiding walks, and we examine the effect that self-attraction has both on the statistics of trapping as well as on chain statistics through the transition between expanded and collapsed walks at the theta point.

Equilibrium structure and deformation response of 2D kinetoplast sheets.

The considerable interest in two-dimensional (2D) materials and complex molecular topologies calls for a robust experimental system for single-molecule studies. In this work, we study the equilibrium properties and deformation response of a complex DNA structure called a kinetoplast, a 2D network of thousands of linked rings akin to molecular chainmail. Examined in good solvent conditions, kinetoplasts appear as a wrinkled hemispherical sheet.

Long-Lived Self-Entanglements in Ring Polymers.

The entanglement of ring polymers remains mysterious in many aspects. In this Letter, we use electric fields to induce self-entanglements in circular DNA molecules, which serve as a minimal system for studying chain entanglements. We show that self-threadings give rise to entanglements in ring polymers and can slow down polymer dynamics significantly.

Conformational State Hopping of Knots in Tensioned Polymer Chains.

We use Brownian dynamics simulations to study the conformational states of knots on tensioned chains. Focusing specifically on the 8 knot, we observe knot conformational state hopping and show that the process can be described by a two-state kinetic model in the presence of an external force. The distribution of knot conformational states depends on the applied chain tension, which leads to a force-dependent distribution of knot untying pathways.

Chlorosis as a Developmental Program in Cyanobacteria: The Proteomic Fundament for Survival and Awakening.

Cyanobacteria that do not fix atmospheric nitrogen gas survive prolonged periods of nitrogen starvation in a chlorotic, dormant state where cell growth and metabolism are arrested. Upon nutrient availability, these dormant cells return to vegetative growth within 2-3 days. This resuscitation process is highly orchestrated and relies on the stepwise reinstallation and activation of essential cellular structures and functions.

Motion of Knots in DNA Stretched by Elongational Fields.

Knots in DNA occur in biological systems, serve as a model system for polymer entanglement, and affect the efficacy of modern genomics technologies. We study the motion of complex knots in DNA by stretching molecules with a divergent electric field that provides an elongational force. We demonstrate that the motion of knots is nonisotropic and driven towards the closest end of the molecule.

A Specific Glycogen Mobilization Strategy Enables Rapid Awakening of Dormant Cyanobacteria from Chlorosis.

Many organisms survive stressful conditions via entry into a dormant state that can be rapidly exited when the stressor disappears; this ability provides a strong selective advantage. In the cyanobacterium sp. PCC 6803, the exit from nitrogen chlorosis takes less than 48 h and is enabled by the impressive metabolic flexibility of these cyanobacteria, which pass through heterotrophic and mixotrophic phases before reentering photoautotrophic growth.

Knots modify the coil-stretch transition in linear DNA polymers.

We perform single-molecule DNA experiments to investigate the relaxation dynamics of knotted polymers and examine the steady-state behavior of knotted polymers in elongational fields. The occurrence of a knot reduces the relaxation time of a molecule and leads to a shift in the molecule's coil-stretch transition to larger strain rates. We measure chain extension and extension fluctuations as a function of strain rate for unknotted and knotted molecules.

Steady-State and Transient Behavior of Knotted Chains in Extensional Fields.

Recently, there has been a push to understand how molecular topology alters the nonequilibrium dynamics of polymer systems. In this paper, we probe how knotted polymers evolve in planar extensional fields using Brownian dynamics simulations and single-molecule experiments. In the first part of the study, we quantify the extension versus strain-rate curves of polymers and find that knots shift these curves to larger strain-rates.

Nanoconfinement greatly speeds up the nucleation and the annealing in single-DNA collapse.

Manipulating and measuring single-molecule dynamics and reactions in nanofluidics is a rapidly growing field with broad applications in developing new biotechnologies, understanding nanoconfinement effects in vivo, and exploring new phenomena in confinement. In this work, we investigate the kinetics of DNA collapse in nanoslits using single T4-DNA (165.6 kbp) and λ-DNA (48.

Waves of DNA: Propagating excitations in extended nanoconfined polymers.

We use a nanofluidic system to investigate the emergence of thermally driven collective phenomena along a single polymer chain. In our approach, a single DNA molecule is confined in a nanofluidic slit etched with arrays of embedded nanocavities; the cavity lattice is designed so that a single chain occupies multiple cavities. Fluorescent video-microscopy data shows fluctuations in intensity between cavities, including waves of excess fluorescence that propagate across the cavity-straddling molecule, corresponding to propagating fluctuations of contour overdensity in the cavities.

Awakening of a Dormant Cyanobacterium from Nitrogen Chlorosis Reveals a Genetically Determined Program.

The molecular and physiological mechanisms involved in the transition of microbial cells from a resting state to the active vegetative state are critically relevant for solving problems in fields ranging from microbial ecology to infection microbiology. Cyanobacteria that cannot fix nitrogen are able to survive prolonged periods of nitrogen starvation as chlorotic cells in a dormant state. When provided with a usable nitrogen source, these cells re-green within 48 hr and return to vegetative growth.

Improving the drug development process by reducing the impact of adverse events: the case of cataracts considered.

Cataract was used as a model for the prevalence and economic impact of adverse events during the drug development process. Meta-analysis revealed a reported prevalence of cataract at 12.0% (1.

Photoautotrophic Polyhydroxybutyrate Granule Formation Is Regulated by Cyanobacterial Phasin PhaP in Synechocystis sp. Strain PCC 6803.

Cyanobacteria are photoautotrophic microorganisms which fix atmospheric carbon dioxide via the Calvin-Benson cycle to produce carbon backbones for primary metabolism. Fixed carbon can also be stored as intracellular glycogen, and in some cyanobacterial species like Synechocystis sp. strain PCC 6803, polyhydroxybutyrate (PHB) accumulates when major nutrients like phosphorus or nitrogen are absent.