Self-generated Gradients Research Articles

N-Type Nanocomposite Films Combining SWCNTs, Bi2Te3 Nanoplates, and Cationic Surfactant for Pn-Junction Thermoelectric Generators with Self-Generated Temperature Gradient Under Uniform Sunlight Irradiation

N-Type Nanocomposite Films Combining SWCNTs, Bi2Te3 Nanoplates, and Cationic Surfactant for Pn-Junction Thermoelectric Generators with Self-Generated Temperature Gradient Under Uniform Sunlight Irradiation

Collective durotaxis along a self-generated mobile stiffness gradient in vivo

A crucial aspect of tissue self-organization during morphogenesis, wound healing, and cancer invasion is directed migration of cell collectives. The majority of in vivo directed migration has been guided by chemotaxis, whereby cells follow a chemical gradient. In certain situations, migrating cell collectives can also self-generate the stiffness gradient in the surrounding tissue, which can have a feedback effect on the directionality of the migration. The phenomenon has been observed during collective durotaxis in vivo. Along the biointerface between neighbouring tissues, heterotypic cell-cell interactions are the main cause of this self-generated stiffness gradient. The physical processes in charge of tissue self-organization along the biointerface, which are related to the interplay between cell signalling and the formation of heterotypic cell-cell adhesion contacts, are less well-developed than the biological mechanisms of the cellular interactions.This complex phenomenon is discussed here in the model system, such as collective migration of neural crest cells between ectodermal placode and mesoderm subpopulations within Xenopus embryos by pointing to the role of the dynamics along the biointerface between adjacent cell subpopulations on the subpopulation stiffness.

Oxidized Low-Density Lipoprotein: Preparation, Validation, and Use in Cell Models.

Lipoproteins in plasma are constituted by the least dense chylomicron, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) that can be separated using commercially available medium such as iodixanol. Iodixanol constitutes the self-generated density gradient to fractionate lipoproteins by rapid ultracentrifugation method, replacing time-consuming protocols. Filling the centrifuge tubes is technically easier and faster than layering salt gradients and is reproducible. The separated lipoproteins by this method are closest to the native state with 80 to 100% recovery possible. Low-density lipoprotein is the major carrier of cholesterol in systemic circulation. The plasma isolated LDL is purified to be used as native LDL and for the preparation of oxidized LDL (oxLDL). The oxLDL is characterized for its oxidation, by various methods based on assay of the lipid and protein oxidation products such as TBARS, conjugated diene formation, and by other methods such as agarose gel electrophoresis. Rapid isolation of LDL particles from human plasma is useful for lipid peroxidation studies, characterization of subclass for functional studies and clinical correlation especially in cardiovascular diseases apart from lipidomic, and proteomic studies. OxLDL preparations are done in vitro chiefly based on copper-induced oxidation; glucose and other prooxidants. Which are used for various studies using animal model and in vitro cell modelsespecially to understand macrophage-mediated atheroma formation, vascular endothelial cell dysfunction, cell signaling studies has scope for extensive researchin metabolic dysfunction of various cells.This chapter deals with one of the applications in the in vitro cell models using macrophage (THP-1 cell line) and human retinal pigment epithelial cell (ARPE-19 cell line) to study the oxLDL uptake using fluorescently labeled oxidized LDL (DiI-oxLDL).

Microfluidic devices for precise measurements of cell directionality reveal a role for glutamine during cell migration

Cancer cells that migrate from tumors into surrounding tissues are responsible for cancer dissemination through the body. Microfluidic devices have been instrumental in discovering unexpected features of cancer cell migration, including the migration in self-generated gradients and the contributions of cell–cell contact during collective migration. Here, we design microfluidic channels with five successive bifurcations to characterize the directionality of cancer cell migration with high precision. We uncover an unexpected role for glutamine in epithelial cancer cell orientation, which could be replaced by alfa-keto glutarate but not glucose.

Open Questions of Chemically Powered Nano- and Micromotors.

Chemically powered nano- and micromotors are microscopic devices that convert chemical energy into motion. Interest in these motors has grown over the past 20 years because they exhibit interesting collective behaviors and have found potential uses in biomedical and environmental applications. Understanding how these motors operate both individually and collectively and how environments affect their operation is of both fundamental and applied significance. However, there are still significant gaps in our knowledge. This Perspective highlights several open questions regarding the propulsion mechanisms of, interactions among, and impact of confinements on nano- and micromotors driven by self-generated chemical gradients. These questions are based on my own experience as an experimentalist. For each open question, I describe the problem and its significance, analyze the status-quo, identify the bottleneck problem, and propose potential solutions. An underlying theme for these questions is the interplay among reaction kinetics, physicochemical distributions, and fluid flows. Unraveling this interplay requires careful measurements as well as a close collaboration between experimentalists and theoreticians/numerical experts. The interdisciplinary nature of these challenges suggests that their solutions could bring new revelations and opportunities across disciplines such as colloidal sciences, material sciences, soft matter physics, robotics, and beyond.

CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration.

Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein-coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization.

Positive Chemotaxis of CREKA-Modified Ceria@Polydopamine Biomimetic Nanoswimmers for Enhanced Penetration and Chemo-photothermal Tumor Therapy.

Tumor interstitial pressure represents the greatest barrier against drug diffusion into the depth of the tumor. Biometric nanomotors highlight the possibility of enhanced deep penetration and improve cellular uptake. However, control of their directionality remains difficult to achieve. Herein, we report cysteine-arginine-glutamic acid-lysine-alanine (CREKA)-modified ceria@polydopamine nanobowls as tumor microenvironment-fueled nanoscale motors for positive chemotaxis into the tumor depth or toward tumor cells. Upon laser irradiation, this nanoswimmer rapidly depletes the tumor microenvironment-specific hydrogen peroxide (H2O2) in the nanobowl, contributing to a self-generated gradient and subsequently propulsion (9.5 μm/s at 46 °C). Moreover, the asymmetrical modification of CREKA on nanobowls could automatically reconfigure the motion direction toward tumor depth or tumor cells in response to receptor-ligand interaction, leading to a deep penetration (70 μm in multicellular spheroids) and enhanced antitumor effects over conventional nanomedicine-induced chemo-photothermal therapy (tumor growth inhibition rate: 84.2% versus 56.9%). Thus, controlling the direction of nanomotors holds considerable potential for improved antitumor responses, especially in solid tumors with high tumor interstitial pressure.

Self-Solidifying Active Droplets Showing Memory-Induced Chirality.

Most synthetic microswimmers do not reach the autonomy of their biological counterparts in terms of energy supply and diversity of motions. Here, this work reports the first all-aqueous droplet swimmer powered by self-generated polyelectrolyte gradients, which shows memory-induced chirality while self-solidifying. An aqueous solution of surface tension-lowering polyelectrolytes self-solidifies on the surface of acidic water, during which polyelectrolytes are gradually emitted into the surrounding water and induce linear self-propulsion via spontaneous symmetry breaking. The low diffusion coefficient of the polyelectrolytes leads to long-lived chemical trails which cause memory effects that drive a transition from linear to chiral motion without requiring any imposed symmetry breaking. The droplet swimmer is capable of highly efficient removal (up to 85%) of uranium from aqueous solutions within 90min, benefiting from self-propulsion and flow-induced mixing. These results provide a route to fueling self-propelled agents which can autonomously perform chiral motion and collect toxins.

The interplay between chemo-phoretic interactions and crowding in active colloids.

Many motile microorganisms communicate with each other and their environments via chemical signaling which leads to long-range interactions mediated by self-generated chemical gradients. However, consequences of the interplay between crowding and chemotactic interactions on their collective behavior remain poorly understood. In this work, we use Brownian dynamics simulations to investigate the effect of packing fraction on the formation of non-equilibrium structures in a monolayer of diffusiophoretic self-propelled colloids as a model for chemically active particles. Focusing on the case when a chemical field induces attractive positional and repulsive orientational interactions, we explore dynamical steady-states of active colloids of varying packing fractions and degrees of motility. In addition to collapsed, active gas, and dynamical clustering steady-states reported earlier for low packing fractions, a new phase-separated state emerges. The phase separation results from a competition between long-range diffusiophoretic interactions and motility and is observed at moderate activities and a wide range of packing fractions. Our analysis suggests that the fraction of particles in the largest cluster is a suitable order parameter for capturing the transition from an active gas and dynamical clustering states to a phase-separated state.

Self-generated exclusion zone in a dead-end pore microfluidic channel.

Particles can be manipulated by gradients of concentration (diffusiophoresis) and electric potential (electrophoresis) to transport them to desired locations. To establish these gradients, external stimuli are usually required. In this work, we manipulate particles through a self-generated concentration gradient within a PDMS-based microfluidic platform, without directly applying an external field. The interfacial chemistry of the PDMS results in a local increase of hydronium ions, leading to a concentration and electrical potential gradient in the system, which in turn generate a temporary exclusion zone at the pore entrance, extending up to half of the main channel, or 150 μm. With time, this exclusion zone diminishes as equilibrium in the ion concentration is reached. We study the dynamics of the exclusion zone thickness and find that the Sherwood number determines the size and stability of the exclusion zone. Our work shows, that even without introducing external ionic gradients, particle diffusiophoresis is significant in lab-on-a-chip systems. The interfacial chemistry of the microfluidic platform can have a significant influence on particle movement and this should be considered when designing experiments on diffusiophoresis. The observed phenomenon can be employed to design lab-on-a-chip-based sorting of colloidal particles.

High-throughput imaging and quantitative analysis uncovers the nature of plasmid positioning by ParABS.

The faithful segregation and inheritance of bacterial chromosomes and low-copy number plasmids requires dedicated partitioning systems. The most common of these, ParABS, consists of ParA, a DNA-binding ATPase and ParB, a protein that binds to centromeric-like <i>parS</i> sequences on the DNA cargo. The resulting nucleoprotein complexes are believed to move up a self-generated gradient of nucleoid-associated ParA. However, it remains unclear how this leads to the observed cargo positioning and dynamics. In particular, the evaluation of models of plasmid positioning has been hindered by the lack of quantitative measurements of plasmid dynamics. Here, we use high-throughput imaging, analysis and modelling to determine the dynamical nature of these systems. We find that F plasmid is actively brought to specific subcellular home positions within the cell with dynamics akin to an over-damped spring. We develop a unified stochastic model that quantitatively explains this behaviour and predicts that cells with the lowest plasmid concentration transition to oscillatory dynamics. We confirm this prediction for F plasmid as well as a distantly-related ParABS system. Our results indicate that ParABS regularly positions plasmids across the nucleoid but operates just below the threshold of an oscillatory instability, which according to our model, minimises ATP consumption. Our work also clarifies how various plasmid dynamics are achievable in a single unified stochastic model. Overall, this work uncovers the dynamical nature of plasmid positioning by ParABS and provides insights relevant for chromosome-based systems.

A self-generated Toddler gradient guides mesodermal cell migration.

The sculpting of germ layers during gastrulation relies on the coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor–based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo.

Steering yourself by the bootstraps: how cells create their own gradients for chemotaxis.

Chemotaxis, where cell movement is steered by chemical gradients, is a widespread and essential way of organising cell behaviour. But where do the instructions come from - who makes gradients, and how are they controlled? We discuss the emerging concept that chemotactic cells often create attractant gradients at the same time as responding to them. This self-guidance is more robust, works across greater distances, and is more informative about the local environment than passive responses. Several mechanisms can establish autonomous gradients. Best known are self-generated gradients, in which the cells degrade a widespread attractant, but cells also produce repellents and 'relay' by secreting fresh attractant after stimulation. Understanding how cells make and interpret their own chemoattractant gradients is fundamental to understanding the spatial patterns seen in all organisms.

Chemotactic self-caging in active emulsions

A common feature of biological self-organization is how active agents communicate with each other or their environment via chemical signaling. Such communications, mediated by self-generated chemical gradients, have consequences for both individual motility strategies and collective migration patterns. Here, in a purely physicochemical system, we use self-propelling droplets as a model for chemically active particles that modify their environment by leaving chemical footprints, which act as chemorepulsive signals to other droplets. We analyze this communication mechanism quantitatively both on the scale of individual agent-trail collisions as well as on the collective scale where droplets actively remodel their environment while adapting their dynamics to that evolving chemical landscape. We show in experiment and simulation how these interactions cause a transient dynamical arrest in active emulsions where swimmers are caged between each other's trails of secreted chemicals. Our findings provide insight into the collective dynamics of chemically active particles and yield principles for predicting how negative autochemotaxis shapes their navigation strategy.

Self-generated gradients steer collective migration on viscoelastic collagen networks.

Growing evidence suggests that the physical properties of the cellular microenvironment influence cell migration. However, it is not currently understood how active physical remodelling by cells affects migration dynamics. Here we report that cell clusters seeded on deformable collagen-I networks display persistent collective migration despite not showing any apparent intrinsic polarity. Clusters generate transient gradients in collagen density and alignment due to viscoelastic relaxation of the collagen networks. Combining theory and experiments, we show that crosslinking collagen networks or reducing cell cluster size results in reduced network deformation, shorter viscoelastic relaxation time and smaller gradients, leading to lower migration persistence. Traction force and Brillouin microscopy reveal asymmetries in force distributions and collagen stiffness during migration, providing evidence of mechanical cross-talk between cells and their substrate during migration. This physical model provides a mechanism for self-generated directional migration on viscoelastic substrates in the absence of internal biochemical polarity cues.

Preparation of Ti-Al-Si Gradient Coating Based on Silicon Concentration Gradient and Added-Ce

Titanium and titanium alloys have excellent physical properties and process properties and are widely used in the aviation industry, but their high-temperature oxidation resistance is poor, and there is a thermal barrier temperature of 600 °C, which limits their application as high-temperature components. The Self-generated Gradient Hot-dipping Infiltration (SGHDI) method is used to prepare the Ti-Al-Si gradient coating based on the silicon concentration with a compact Ti(Al,Si)3 phase layer, which can effectively improve the high-temperature oxidation resistance of the titanium alloy. Adding cerium can effectively inhibit the generation of the τ2: Ti(AlxSi1−x)2 phase within a certain hot infiltration time so as to form a continuous dense Al2O3 layer to further improve the oxidation resistance of the coating. Studies have found that multiple Ti-Al binary alloy phase layers are formed during the high-temperature oxidation process, which has the effect of isolating oxygen and crack growth, and effectively improving the high-temperature resistance of the coating oxidation performance.

Nutrient Gradients Mediate Complex Colony-Level Antibiotic Responses in Structured Microbial Populations.

Antibiotic treatments often fail to eliminate bacterial populations due to heterogeneity in how individual cells respond to the drug. In structured bacterial populations such as biofilms, bacterial metabolism and environmental transport processes lead to an emergent phenotypic structure and self-generated nutrient gradients toward the interior of the colony, which can affect cell growth, gene expression and susceptibility to the drug. Even in single cells, survival depends on a dynamic interplay between the drug’s action and the expression of resistance genes. How expression of resistance is coordinated across populations in the presence of such spatiotemporal environmental coupling remains elusive. Using a custom microfluidic device, we observe the response of spatially extended microcolonies of tetracycline-resistant E. coli to precisely defined dynamic drug regimens. We find an intricate interplay between drug-induced changes in cell growth and growth-dependent expression of resistance genes, resulting in the redistribution of metabolites and the reorganization of growth patterns. This dynamic environmental feedback affects the regulation of drug resistance differently across the colony, generating dynamic phenotypic structures that maintain colony growth during exposure to high drug concentrations and increase population-level resistance to subsequent exposures. A mathematical model linking metabolism and the regulation of gene expression is able to capture the main features of spatiotemporal colony dynamics. Uncovering the fundamental principles that govern collective mechanisms of antibiotic resistance in spatially extended populations will allow the design of optimal drug regimens to counteract them.

Cellular Sensing Governs the Stability of Chemotactic Fronts.

In contexts ranging from embryonic development to bacterial ecology, cell populations migrate chemotactically along self-generated chemical gradients, often forming a propagating front. Here, we theoretically show that the stability of such chemotactic fronts to morphological perturbations is determined by limitations in the ability of individual cells to sense and thereby respond to the chemical gradient. Specifically, cells at bulging parts of a front are exposed to a smaller gradient, which slows them down and promotes stability, but they also respond more strongly to the gradient, which speeds them up and promotes instability. We predict that this competition leads to chemotactic fingering when sensing is limited at too low chemical concentrations. Guided by this finding and by experimental data on E. coli chemotaxis, we suggest that the cells' sensory machinery might have evolved to avoid these limitations and ensure stable front propagation. Finally, as sensing of any stimuli is necessarily limited in living and active matter in general, the principle of sensing-induced stability may operate in other types of directed migration such as durotaxis, electrotaxis, and phototaxis.

Chemotactic smoothing of collective migration.

Collective migration-the directed, coordinated motion of many self-propelled agents-is a fascinating emergent behavior exhibited by active matter with functional implications for biological systems. However, how migration can persist when a population is confronted with perturbations is poorly understood. Here, we address this gap in knowledge through studies of bacteria that migrate via directed motion, or chemotaxis, in response to a self-generated nutrient gradient. We find that bacterial populations autonomously smooth out large-scale perturbations in their overall morphology, enabling the cells to continue to migrate together. This smoothing process arises from spatial variations in the ability of cells to sense and respond to the local nutrient gradient-revealing a population-scale consequence of the manner in which individual cells transduce external signals. Altogether, our work provides insights to predict, and potentially control, the collective migration and morphology of cellular populations and diverse other forms of active matter.

Effects of Carbon Additions on the Ti-Al-Si Coating Synthesized by Self-Generated Gradient Hot-Dipping Infiltration Method

Effects of Carbon Additions on the Ti-Al-Si Coating Synthesized by Self-Generated Gradient Hot-Dipping Infiltration Method