Collective chemomechanical oscillations in active hydrogels.

We report on the collective response of an assembly of chemomechanical Belousov-Zhabotinsky (BZ) hydrogel beads. We first demonstrate that a single isolated spherical BZ hydrogel bead with a radius below a critical value does not oscillate, whereas an assembly of the same BZ hydrogel beads presents chemical oscillation. A BZ chemical model with an additional flux of chemicals out of the BZ hydrogel captures the experimentally observed transition from oxidized nonoscillating to oscillating BZ hydrogels and shows this transition is due to a flux of inhibitors out of the BZ hydrogel. The model also captures the role of neighboring BZ hydrogel beads in decreasing the critical size for an assembly of BZ hydrogel beads to oscillate. We finally leverage the quorum sensing behavior of the collective to trigger their chemomechanical oscillation and discuss how this collective effect can be used to enhance the oscillatory strain of these active BZ hydrogels. These findings could help guide the eventual fabrication of a swarm of autonomous, communicating, and motile hydrogels.

Innate IRE1α-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia.

The utilization of host-cell machinery during SARS-CoV-2 infection can overwhelm the protein-folding capacity of the endoplasmic reticulum and activate the unfolded protein response (UPR). The IRE1α-XBP1 arm of the UPR could also be activated by viral RNA via Toll-like receptors. Based on these premises, a study to gain insight into the pathogenesis of COVID-19 disease was conducted using nasopharyngeal exudates and bronchioloalveolar aspirates. The presence of the mRNA of spliced XBP1 and a high expression of cytokine mRNAs were observed during active infection. TLR8 mRNA showed an overwhelming expression in comparison with TLR7 mRNA in bronchioloalveolar aspirates of COVID-19 patients, thus suggesting the presence of monocytes and monocyte-derived dendritic cells (MDDCs). In vitro experiments in MDDCs activated with ssRNA40, a synthetic mimic of SARS-CoV-2 RNA, showed induction of XBP1 splicing and the expression of proinflammatory cytokines. These responses were blunted by the IRE1α inhibitor MKC8866, the TLR8 antagonist CU-CPT9a, and knockdown of TLR8 receptor. In contrast, the IRE1α-XBP1 activator IXA4 enhanced these responses. Based on these findings, the TLR8/IRE1α system seems to play a significant role in the induction of the proinflammatory cytokines associated with severe COVID-19 disease and might be a druggable target to control cytokine storm.

Active many-particle systems and the emergent behavior of dense ant collectives.

This article discusses recent work with fire ants,Solenopisis invicta, to illustrate the use of the framework of active matter as a base to rationalize their complex collective behavior. We review much of the work that physicists have done on the group dynamics of these ants, and compare their behavior to two minimal models of active matter, and to the behavior of the synthetic systems that have served to test and drive these models.

First Order Alignment Transition in an Interfaced Active Nematic Fluid.

We investigate experimentally the dynamic phase transition of a two-dimensional active nematic layer interfaced with a passive liquid crystal. Under a temperature ramp that leads to the transition of the passive liquid into a highly anisotropic lamellar smectic-A phase, and in the presence of a magnetic field, the coupled active nematic reorganizes its flow and orientational patterns from the turbulent into a quasilaminar regime aligned perpendicularly to the field. Remarkably, while the phase transition of the passive fluid is known to be continuous, or second order, our observations reveal intermittent dynamics of the order parameter and the coexistence of aligned and turbulent regions in the active nematic, a signature of discontinuous, or first order, phase transitions, similar to what is known to occur in relation to flocking in dry active matter. Our results suggest that alignment transitions in active systems are intrinsically discontinuous, regardless of the symmetry and momentum-damping mechanisms.

Fungal Patterns Induce Cytokine Expression through Fluxes of Metabolic Intermediates That Support Glycolysis and Oxidative Phosphorylation.

Cytokine expression is fine-tuned by metabolic intermediates, which makes research on immunometabolism suitable to yield drugs with a wider prospect of application than the biological therapies that block proinflammatory cytokines. Switch from oxidative phosphorylation (OXPHOS) to glycolysis has been considered a characteristic feature of activated immune cells. However, some stimuli might enhance both routes concomitantly. The connection between the tricarboxylic acid cycle and cytokine expression was scrutinized in human monocyte-derived dendritic cells stimulated with the fungal surrogate zymosan. Results showed that nucleocytosolic citrate and ATP-citrate lyase activity drove IL1B, IL10, and IL23A expression by yielding acetyl-CoA and oxaloacetate, with the latter one supporting glycolysis and OXPHOS by maintaining cytosolic NAD+ and mitochondrial NADH levels through mitochondrial shuttles. Succinate dehydrogenase showed a subunit-specific ability to modulate IL23A and IL10 expression. Succinate dehydrogenase A subunit activity supported cytokine expression through the control of the 2-oxoglutarate/succinate ratio, whereas C and D subunits underpinned cytokine expression by conveying electron flux from complex II to complex III of the electron transport chain. Fatty acids may also fuel the tricarboxylic acid cycle and influence cytokine expression. Overall, these results show that fungal patterns support cytokine expression through a strong boost of glycolysis and OXPHOS supported by the use of pyruvate, citrate, and succinate, along with the compartmentalized NAD(H) redox state maintained by mitochondrial shuttles.

Long term phase separation dynamics in liquid crystal-enriched microdroplets obtained from binary fluid mixtures.

The dynamics of long term phase separation in binary liquid mixtures remains a subject of fundamental interest. Here, we study a binary liquid mixture, where the minority phase is confined to a liquid crystal (LC)-rich droplet, by investigating the evolution of size, defect and mesogen alignment over time. We track the binary liquid mixture evolving towards equilibrium by visualising the configuration of the liquid crystal droplet through polarisation microscopy. We compare our experimental findings with computational simulations and elucidate differences between bulk phases and confined droplets based on the respective thermodynamics of phase separation. Our work provides insights on how phase transitions on the microscale can deviate from bulk phase diagrams with relevance to other material systems, such as the liquid-liquid phase separation of polymer and protein solutions.

Behavior and mechanics of dense microgel suspensions.

Suspensions of soft and highly deformable microgels can be concentrated far more than suspensions of hard colloids, leading to their unusual mechanical properties. Microgels can accommodate compression in suspensions in a variety of ways such as interpenetration, deformation, and shrinking. Previous experiments have offered insightful, but somewhat conflicting, accounts of the behavior of individual microgels in compressed suspensions. We develop a mesoscale computational model to probe the behavior of compressed suspensions consisting of microgels with different architectures at a variety of packing fractions and solvent conditions. We find that microgels predominantly change shape and mildly shrink above random close packing. Interpenetration is only appreciable above space filling, remaining small relative to the mean distance between cross-links. At even higher packing fractions, microgels solely shrink. Remarkably, irrespective of the single-microgel properties, and whether the suspension concentration is changed via changing the particle number density or the swelling state of the particles, which can even result in colloidal gelation, the mechanics of the suspension can be quantified in terms of the single-microgel bulk modulus, which thus emerges as the correct mechanical measure for these type of soft-colloidal suspensions. Our results rationalize the many and varied experimental results, providing insights into the relative importance of effects defining the mechanics of suspensions comprising soft particles.

Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts.

BACKGROUND: The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS), i.e. fever, cough and loss or change in smell or taste, could improve case definitions and accelerate case identification in SARS-CoV-2 contacts. METHODS: Two prospective longitudinal London (UK)-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and area under the receiver operating characteristic curve. Improvements in sensitivity and time to detection were compared with penalties in terms of specificity and number needed to test. RESULTS: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion "≥1 of the CS, or ≥2 of the EP" identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than "≥1 of the CS", with only modest reduction in specificity (5.7%). CONCLUSIONS: Broadening symptom criteria to include individuals with at least two of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time to detection, providing greater opportunities to prevent SARS-CoV-2 transmission.

From nematic shells to nematic droplets: energetics and defect transitions.

In this work, we investigate the possibility of inducing valence transitions, i.e. transitions between different defect configurations, by transforming a nematic shell into a nematic droplet. Our shells are liquid crystal droplets containing a smaller aqueous droplet inside, which are suspended in an aqueous phase. When osmotically de-swelling the inner droplet, the shell progressively increases its thickness until it eventually becomes a single droplet. During the process, the shell energy landscape evolves, triggering a response in the system. We observe two different scenarios. Either the inner droplet progressively shrinks and disappears, inducing a defect reorganization, or it is expelled from the shell at a critical radius of the inner droplet, abruptly changing the geometry of the system. We use numerical simulations and modeling to investigate the origin of these behaviors. We find that the selected route depends on the defect structure and the energetics of the system as it evolves. The critical inner radius and time for expulsion depend on the osmotic pressure of the outer phase, suggesting that the flow through the shell plays a role in the process.

Orientational Correlations in Active and Passive Nematic Defects.

We investigate the emergence of orientational order among +1/2 disclinations in active nematic liquid crystals. Using a combination of theoretical and experimental methods, we show that +1/2 disclinations have short-range antiferromagnetic alignment, as a consequence of the elastic torques originating from their polar structure. The presence of intermediate -1/2 disclinations, however, turns this interaction from antialigning to aligning at scales that are smaller than the typical distance between like-sign defects. No long-range orientational order is observed. Strikingly, these effects are insensitive to material properties and qualitatively similar to what is found for defects in passive nematic liquid crystals.

Capillary-Based Microfluidics-Coflow, Flow-Focusing, Electro-Coflow, Drops, Jets, and Instabilities.

Capillary-based microfluidics is a great technique to produce monodisperse and complex emulsions and particulate suspensions. In this review, the current understanding of drop and jet formation in capillary-based microfluidic devices for two primary flow configurations, coflow and flow-focusing is summarized. The experimental and theoretical description of fluid instabilities is discussed and conditions for controlled drop breakup in different modes of drop generation are provided. Current challenges in drop breakup with low interfacial tension systems and recent progress in overcoming drop size limitations using electro-coflow are addressed. In each scenario, the physical mechanisms for drop breakup are revisited, and simple scaling arguments proposed in the literature are introduced.

Reverse Janssen Effect in Narrow Granular Columns.

When grains are added to a cylinder, the weight at the bottom is smaller than the total weight of the column, which is partially supported by the lateral walls through frictional interactions with the grains. This is known as the Janssen effect. Via a combined experimental and numerical investigation, here we demonstrate a reverse Jansen effect whereby the fraction of the weight supported by the base overcomes one. We characterize the dependence of this phenomenon on the various control parameters involved, rationalize the physical process causing the emergence of the compressional frictional forces responsible for the anomaly, and introduce a model to reproduce our findings. Contrary to prior assumptions, our results demonstrate that the constitutive relation on a material element can depend on the applied stress.

Rheology of capillary foams.

Aqueous foams are ubiquitous; they appear in products and processes that span the cosmetics, food, and energy industries. The versatile applicability of foams comes as a result of their intrinsic viscous and elastic properties; for example, foams are exploited as drilling fluids in enhanced oil recovery for their high viscosity. Recently, so-called capillary foams were discovered: a class of foams that have excellent stability under static conditions and whose flow properties have so far remained unexplored. The unique architecture of these foams, containing oil-coated bubbles and a gelled network of oil-bridged particles, is expected to affect foam rheology. In this work, we report the first set of rheological data on capillary foams. We study the viscoelastic properties of capillary foams by conducting oscillatory and steady shear tests. We compare our results on the rheological properties of capillary foams to those reported for other aqueous foams. We find that capillary foams, which have low gas volume fractions, exhibit long lasting rheological stability as well as a yielding behavior that is reminiscent of surfactant foams with high gas volume fractions.

Complexation of Pluronic L62 (EO6)-(PO34)-(EO6)/aerosol-OT (sodium bis(2-ethylhexyl)sulfosuccinate) in aqueous solutions investigated by small angle neutron scattering.

We investigate the phase behaviours of Pluronic L62 in aqueous solution in the presence of aerosol-OT (AOT) molecules by small angle neutron scattering (SANS). The presence of AOT significantly changes the micellization phenomenon of L62 micelles in aqueous solution, including their critical micelle temperature (CMT), global size, and asphericity. The origin of these observations is attributed to the complexation between the neutral L62 surfactants and the ionic AOT molecules, which additionally provides charge to the mixed micelles: we analyse the data and extract meaningful information using the Ornstein-Zernike integral formalism. As a result, we observe that the co-micellization of L62 and AOT is very stable across a wide temperature range.

Shrinking instability of toroidal droplets.

Toroidal droplets are inherently unstable due to surface tension. They can break up, similar to cylindrical jets, but also exhibit a shrinking instability, which is inherent to the toroidal shape. We investigate the evolution of shrinking toroidal droplets using particle image velocimetry. We obtain the flow field inside the droplets and show that as the torus evolves, its cross-section significantly deviates from circular. We then use the experimentally obtained velocities at the torus interface to theoretically reconstruct the internal flow field. Our calculation correctly describes the experimental results and elucidates the role of those modes that, among the many possible ones, are required to capture all of the relevant experimental features.

Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers.

In regenerative medicine, natural protein-based polymers offer enhanced endogenous bioactivity and potential for seamless integration with tissue, yet form weak hydrogels that lack the physical robustness required for surgical manipulation, making them difficult to apply in practice. The use of higher concentrations of protein, exogenous cross-linkers, and blending synthetic polymers has all been applied to form more mechanically robust networks. Each relies on generating a smaller network mesh size, which increases the elastic modulus and robustness, but critically inhibits cell spreading and migration, hampering tissue regeneration. Here we report two unique observations; first, that colloidal suspensions, at sufficiently high volume fraction (ϕ), dynamically assemble into a fully percolated 3D network within high-concentration protein polymers. Second, cells appear capable of leveraging these unique domains for highly efficient cell migration throughout the composite construct. In contrast to porogens, the particles in our system remain embedded within the bulk polymer, creating a network of particle-filled tunnels. Whereas this would normally physically restrict cell motility, when the particulate network is created using ultralow cross-linked microgels, the colloidal suspension displays viscous behavior on the same timescale as cell spreading and migration and thus enables efficient cell infiltration of the construct through the colloidal-filled tunnels.

Geometrical Control of Active Turbulence in Curved Topographies.

We investigate the turbulent dynamics of a two-dimensional active nematic liquid crystal constrained to a curved surface. Using a combination of hydrodynamic and particle-based simulations, we demonstrate that the fundamental structural features of the fluid, such as the topological charge density, the defect number density, the nematic order parameter, and defect creation and annihilation rates, are approximately linear functions of the substrate Gaussian curvature, which then acts as a control parameter for the chaotic flow. Our theoretical predictions are then compared with experiments on microtubule-kinesin suspensions confined on toroidal droplets, finding excellent qualitative agreement.

Curved boundaries and chiral instabilities - two sources of twist in homeotropic nematic tori.

Many liquid crystalline systems display spontaneous breaking of achiral symmetry, as achiral molecules aggregate into large chiral domains. In confined cylinders with homeotropic boundary conditions, chromonic liquid crystals - which have a twist elastic modulus which is at least an order of magnitude less than their splay and bend counter parts - adopt a twisted escaped radial texture (TER) to minimize their free energy, whilst 5CB - which has all three elastic constants roughly comparable - does not. In a recent series of experiments, we have shown that 5CB confined to tori and bent cylindrical capillaries with homeotropic boundary conditions also adopts a TER structure resulting from the curved nature of the confining boundaries [P. W. Ellis et al., Phys. Rev. Lett., 2018, 247803]. We shall call this microscopic twist, as the twisted director organization not only depends on the confinement geometry but also on the values of elastic moduli. Additionally, we demonstrate theoretically that the curved geometry of the boundary induces a twist in the escaped radial (ER) texture. Moving the escaped core of the structure towards the center of the torus not only lowers the splay and bend energies, but lowers the energetic cost of this distinct source for twist that we shall call geometric twist. As the torus becomes more curved, the ideal location for the escaped core approaches the inner radius of the torus.

The role of ions in the self-healing behavior of soft particle suspensions.

Impurities in crystals generally cause point defects and can even suppress crystallization. This general rule, however, does not apply to colloidal crystals formed by soft microgel particles [Iyer ASJ, Lyon LA (2009) Angew Chem Int Ed 48:4562-4566], as, in this case, the larger particles are able to shrink and join the crystal formed by a majority of smaller particles. Using small-angle X-ray scattering, we find the limit in large-particle concentration for this spontaneous deswelling to persist. We rationalize our data in the context of those counterions that are bound to the microgel particles as a result of the electrostatic attraction exerted by the fixed charges residing on the particle periphery. These bound counterions do not contribute to the suspension osmotic pressure in dilute conditions, as they can be seen as internal degrees of freedom associated with each microgel particle. In contrast, at sufficiently high particle concentrations, the counterion cloud of each particle overlaps with that of its neighbors, allowing these ions to freely explore the space outside the particles. We confirm this scenario by directly measuring the osmotic pressure of the suspension. Because these counterions are then no longer bound, they create an osmotic pressure difference between the inside and outside of the microgels, which, if larger than the microgel bulk modulus, can cause deswelling, explaining why large, soft microgel particles feel the squeeze when suspended with a majority of smaller particles. We perform small-angle neutron scattering measurements to further confirm this remarkable behavior.

Polymorphisms in Receptors Involved in Opsonic and Nonopsonic Phagocytosis, and Correlation with Risk of Infection in Oncohematology Patients.

High-risk hematological malignancies are a privileged setting for infection by opportunistic microbes, with invasive mycosis being one of the most serious complications. Recently, genetic background has emerged as an unanticipated risk factor. For this reason, polymorphisms for genes encoding archetypal receptors involved in the opsonic and nonopsonic clearance of microbes, pentraxin-3 (PTX3) and Dectin-1, respectively, were studied and correlated with the risk of infection. Fungal, bacterial, and viral infections were registered for a group of 198 patients with high-risk hematological malignancies. Polymorphisms for the pentraxin-3 gene (PTX3) showed a significant association with the risk of fungal infection by Candida spp. and, especially, by Aspergillus spp. This link remained even for patients undergoing antifungal prophylaxis, thus demonstrating the clinical relevance of PTX3 in the defense against fungi. CLEC7A polymorphisms did not show any definite correlation with the risk of invasive mycosis, nor did they influence the expression of Dectin-1 isoforms generated by alternative splicing. The PTX3 mRNA expression level was significantly lower in samples from healthy volunteers who showed these polymorphisms, although no differences were observed in the extents of induction elicited by bacterial lipopolysaccharide and heat-killed Candidaalbicans, thus suggesting that the expression of PTX3 at the start of infection may influence the clinical outcome. PTX3 mRNA expression can be a good biomarker to establish proper antifungal prophylaxis in immunodepressed patients.