Cellular Control of Viscosity Counters Changes in Temperature and Energy Availability.

Cellular functioning requires the orchestration of thousands of molecular interactions in time and space. Yet most molecules in a cell move by diffusion, which is sensitive to external factors like temperature. How cells sustain complex, diffusion-based systems across wide temperature ranges is unknown. Here, we uncover a mechanism by which budding yeast modulate viscosity in response to temperature and energy availability. This "viscoadaptation" uses regulated synthesis of glycogen and trehalose to vary the viscosity of the cytosol. Viscoadaptation functions as a stress response and a homeostatic mechanism, allowing cells to maintain invariant diffusion across a 20°C temperature range. Perturbations to viscoadaptation affect solubility and phase separation, suggesting that viscoadaptation may have implications for multiple biophysical processes in the cell. Conditions that lower ATP trigger viscoadaptation, linking energy availability to rate regulation of diffusion-controlled processes. Viscoadaptation reveals viscosity to be a tunable property for regulating diffusion-controlled processes in a changing environment.

Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation.

The formation of silenced and condensed heterochromatin foci involves enrichment of heterochromatin protein 1 (HP1). HP1 can bridge chromatin segments and form liquid droplets, but the biophysical principles underlying heterochromatin compartmentalization in the cell nucleus are elusive. Here, we assess mechanistically relevant features of pericentric heterochromatin compaction in mouse fibroblasts. We find that (1) HP1 has only a weak capacity to form liquid droplets in living cells; (2) the size, global accessibility, and compaction of heterochromatin foci are independent of HP1; (3) heterochromatin foci lack a separated liquid HP1 pool; and (4) heterochromatin compaction can toggle between two "digital" states depending on the presence of a strong transcriptional activator. These findings indicate that heterochromatin foci resemble collapsed polymer globules that are percolated with the same nucleoplasmic liquid as the surrounding euchromatin, which has implications for our understanding of chromatin compartmentalization and its functional consequences.

Viscous shear is a key force in Drosophila ventral furrow morphogenesis.

Ventral furrow (VF) formation in Drosophila melanogaster is an important model of epithelial folding. Previous models of VF formation require cell volume conservation to convert apically localized constriction forces into lateral cell elongation and tissue folding. Here, we investigated embryonic morphogenesis in anillin knockdown (scra RNAi) embryos, where basal cell membranes fail to form and therefore cells can lose cytoplasmic volume through their basal side. Surprisingly, the mesoderm elongation and subsequent folding that comprise VF formation occurred essentially normally. We hypothesized that the effects of viscous shear may be sufficient to drive membrane elongation, providing effective volume conservation, and thus driving tissue folding. Since this hypothesis may not be possible to test experimentally, we turned to a computational approach. To test whether viscous shear is a dominant force for morphogenesis in vivo, we developed a 3D computational model incorporating both accurate cell and tissue geometry and experimentally measured material parameters. Results from this model demonstrate that viscous shear generates sufficient force to drive cell elongation and tissue folding in vivo.

Diagnostic potential of blood plasma longitudinal viscosity measured using Brillouin light scattering.

Blood plasma viscosity (PV) is an established biomarker for numerous diseases. Measurement of the shear PV using conventional rheological techniques is, however, time consuming and requires significant plasma volumes. Here, we show that Brillouin light scattering (BLS) and angle-resolved spectroscopy measurements of the longitudinal PV from microliter-sized plasma volumes can serve as a proxy for the shear PV measured using conventional viscometers. This is not trivial given the distinct frequency regime probed and the longitudinal viscosity, a combination of the shear and bulk viscosity, representing a unique material property on account of the latter. We demonstrate this for plasma from healthy persons and patients suffering from different severities of COVID-19 (CoV), which has been associated with an increased shear PV. We further show that the additional information contained in the BLS-measured effective longitudinal PV and its temperature scaling can provide unique insight into the chemical constituents and physical properties of plasma that can be of diagnostic value. In particular, we find that changes in the effective longitudinal viscosity are consistent with an increased suspension concentration in CoV patient samples at elevated temperatures that is correlated with disease severity and progression. This is supported by results from rapid BLS spatial-mapping, angle-resolved BLS measurements, changes in the elastic scattering, and anomalies in the temperature scaling of the shear viscosity. Finally, we introduce a compact BLS probe to rapidly perform measurements in plastic transport tubes. Our results open a broad avenue for PV diagnostics based on the high-frequency effective longitudinal PV and show that BLS can provide a means for its implementation.

Curvature fluctuations of fluid vesicles reveal hydrodynamic dissipation within the bilayer.

The biological function of membranes is closely related to their softness, which is often studied through the membranes' thermally driven fluctuations. Typically, the analysis assumes that the relaxation rate of a pure bending deformation is determined by the competition between membrane bending rigidity and viscous dissipation in the surrounding medium. Here, we reexamine this assumption and demonstrate that viscous flows within the membrane dominate the dynamics of bending fluctuations of nonplanar membranes with a radius of curvature smaller than the Saffman-Delbrück length. Using flickering spectroscopy of giant vesicles made of dipalmitoylphosphatidylcholine, DPPC:cholesterol mixtures and pure diblock-copolymer membranes, we experimentally detect the signature of membrane dissipation in curvature fluctuations. We show that membrane viscosity can be reliably obtained from the short time behavior of the shape time correlations. The results indicate that the DPPC:cholesterol membranes behave as a Newtonian fluid, while the polymer membranes exhibit more complex rheology. Our study provides physical insights into the time scales of curvature remodeling of biological and synthetic membranes.

Regulation of intercellular viscosity by E-cadherin-dependent phosphorylation of EGFR in collective cell migration.

Collective cell migration is crucial in various physiological processes, including wound healing, morphogenesis, and cancer metastasis. Adherens Junctions (AJs) play a pivotal role in regulating cell cohesion and migration dynamics during tissue remodeling. While the role and origin of the junctional mechanical tension at AJs have been extensively studied, the influence of the actin cortex structure and dynamics on junction plasticity remains incompletely understood. Moreover, the mechanisms underlying stress dissipation at junctions are not well elucidated. Here, we found that the ligand-independent phosphorylation of epithelial growth factor receptor (EGFR) downstream of de novo E-cadherin adhesion orchestrates a feedback loop, governing intercellular viscosity via the Rac pathway regulating actin dynamics. Our findings highlight how the E-cadherin-dependent EGFR activity controls the migration mode of collective cell movements independently of intercellular tension. This modulation of effective viscosity coordinates cellular movements within the expanding monolayer, inducing a transition from swirling to laminar flow patterns while maintaining a constant migration front speed. Additionally, we propose a vertex model with adjustable junctional viscosity, capable of replicating all observed cellular flow phenotypes experimentally.

Nonreciprocity and odd viscosity in chiral active fluids.

Odd viscosity couples stress to strain rate in a dissipationless way. It has been studied in plasmas under magnetic fields, superfluid [Formula: see text], quantum-Hall fluids, and recently in the context of chiral active matter. In most of these studies, odd terms in the viscosity obey Onsager reciprocal relations. Although this is expected in equilibrium systems, it is not obvious that Onsager relations hold in active materials. By directly coarse-graining the kinetic energy and independently using both the Poisson-bracket formalism and a kinetic theory derivation, we find that the appearance of a nonvanishing angular momentum density, which is a hallmark of chiral active materials, necessarily breaks Onsager reciprocal relations. This leads to a non-Hermitian dynamical matrix for the total hydrodynamic momentum and to the appearance of odd viscosity and other nondissipative contributions to the viscosity. Furthermore, by accounting for both the angular momentum density and interactions that lead to odd viscosity, we find regions in the parameter space in which 3D odd mechanical waves propagate and regions in which they are mechanically unstable. The lines separating these regions are continuous lines of exceptional points, suggesting a possible nonreciprocal phase transition.

Direct measurement of the viscoelectric effect in water.

The viscoelectric effect concerns the increase in viscosity of a polar liquid in an electric field due to its interaction with the dipolar molecules and was first determined for polar organic liquids more than 80 y ago. For the case of water, however, the most common polar liquid, direct measurement of the viscoelectric effect is challenging and has not to date been carried out, despite its importance in a wide range of electrokinetic and flow effects. In consequence, estimates of its magnitude for water vary by more than three orders of magnitude. Here, we measure the viscoelectric effect in water directly using a surface force balance by measuring the dynamic approach of two molecularly smooth surfaces with a controlled, uniform electric field between them across highly purified water. As the water is squeezed out of the gap between the approaching surfaces, viscous damping dominates the approach dynamics; this is modulated by the viscoelectric effect under the uniform transverse electric field across the water, enabling its magnitude to be directly determined as a function of the field. We measured a value for this magnitude, which differs by one and by two orders of magnitude, respectively, from its highest and lowest previously estimated values.

Sunlight can convert atmospheric aerosols into a glassy solid state and modify their environmental impacts.

Secondary organic aerosol (SOA) plays a critical, yet uncertain, role in air quality and climate. Once formed, SOA is transported throughout the atmosphere and is exposed to solar UV light. Information on the viscosity of SOA, and how it may change with solar UV exposure, is needed to accurately predict air quality and climate. However, the effect of solar UV radiation on the viscosity of SOA and the associated implications for air quality and climate predictions is largely unknown. Here, we report the viscosity of SOA after exposure to UV radiation, equivalent to a UV exposure of 6 to 14 d at midlatitudes in summer. Surprisingly, UV-aging led to as much as five orders of magnitude increase in viscosity compared to unirradiated SOA. This increase in viscosity can be rationalized in part by an increase in molecular mass and oxidation of organic molecules constituting the SOA material, as determined by high-resolution mass spectrometry. We demonstrate that UV-aging can lead to an increased abundance of aerosols in the atmosphere in a glassy solid state. Therefore, UV-aging could represent an unrecognized source of nuclei for ice clouds in the atmosphere, with important implications for Earth's energy budget. We also show that UV-aging increases the mixing times within SOA particles by up to five orders of magnitude throughout the troposphere with important implications for predicting the growth, evaporation, and size distribution of SOA, and hence, air pollution and climate.

Odd viscosity-induced Hall-like transport of an active chiral fluid.

Broken time-reversal and parity symmetries in active spinner fluids imply a nondissipative "odd viscosity," engendering phenomena unattainable in traditional passive or active fluids. Here we show that the odd viscosity itself can lead to a Hall-like transport when the active chiral fluid flows through a quenched matrix of obstacles, reminiscent of the anomalous Hall effect. The Hall-like velocity depends significantly on the spinner activity and longitudinal flow due to the interplay between odd viscosity and spinner-obstacle collisions. Our findings underscore the importance of odd viscosity in active chiral matter and elucidate its essential role in the anomalous Hall-like effect.

The underlying mechanical properties of membranes tune their ability to fuse.

Membrane fusion is a ubiquitous process associated with a multitude of biological events. Although it has long been appreciated that membrane mechanics plays an important role in membrane fusion, the molecular interplay between mechanics and fusion has remained elusive. For example, although different lipids modulate membrane mechanics differently, depending on their composition, molar ratio, and complex interactions, differing lipid compositions may lead to similar mechanical properties. This raises the question of whether (i) the specific lipid composition or (ii) the average mesoscale mechanics of membranes acts as the determining factor for cellular function. Furthermore, little is known about the potential consequences of fusion on membrane disruption. Here, we use a combination of confocal microscopy, time-resolved imaging, and electroporation to shed light onto the underlying mechanical properties of membranes that regulate membrane fusion. Fusion efficiency follows a nearly universal behavior that depends on membrane fluidity parameters, such as membrane viscosity and bending rigidity, rather than on specific lipid composition. This helps explaining why the charged and fluid membranes of the inner leaflet of the plasma membrane are more fusogenic than their outer counterparts. Importantly, we show that physiological levels of cholesterol, a key component of biological membranes, has a mild effect on fusion but significantly enhances membrane mechanical stability against pore formation, suggesting that its high cellular levels buffer the membrane against disruption. The ability of membranes to efficiently fuse while preserving their integrity may have given evolutionary advantages to cells by enabling their function while preserving membrane stability.

Hemodynamic Characteristics of a Tortuous Microvessel Using High-Fidelity Red Blood Cell Resolved Simulations.

OBJECTIVE: Tortuous microvessels are characteristic of microvascular remodeling associated with numerous physiological and pathological scenarios. Three-dimensional (3D) hemodynamics in tortuous microvessels influenced by red blood cells (RBCs), however, are largely unknown, and important questions remain. Is blood viscosity influenced by vessel tortuosity? How do RBC dynamics affect wall shear stress (WSS) patterns and the near-wall cell-free layer (CFL) over a range of conditions? The objective of this work was to parameterize hemodynamic characteristics unique to a tortuous microvessel. METHODS: RBC-resolved simulations were performed using an immersed boundary method-based 3D fluid dynamics solver. A representative tortuous microvessel was selected from a stimulated angiogenic network obtained from imaging of the rat mesentery and digitally reconstructed for the simulations. The representative microvessel was a venule with a diameter of approximately 20 µm. The model assumes a constant diameter along the vessel length and does not consider variations due to endothelial cell shapes or the endothelial surface layer. RESULTS: Microvessel tortuosity was observed to increase blood apparent viscosity compared to a straight tube by up to 26%. WSS spatial variations in high curvature regions reached 23.6 dyne/cm2 over the vessel cross-section. The magnitudes of WSS and CFL thickness variations due to tortuosity were strongly influenced by shear rate and negligibly influenced by tube hematocrit levels. CONCLUSIONS: New findings from this work reveal unique tortuosity-dependent hemodynamic characteristics over a range of conditions. The results provide new thought-provoking information to better understand the contribution of tortuous vessels in physiological and pathological processes and help improve reduced-order models.

Applied Electric Field Effects on Diffusivity and Electrical Double-Layer Thickness.

This study utilizes molecular dynamics (MD) simulations and continuum frameworks to explore electroosmotic flow (EOF) in nanoconfined aqueous electrolytes, offering a promising alternative to conventional micro-/nanofluidic systems. Although osmotic behavior in these environments is deeply linked to local fluid properties and interfacial dynamics between the fluid and electrolyte solutions, achieving a complete molecular-level understanding has remained challenging. The findings establish a linear relationship between electric field strength and fluid velocity, uncovering two distinct transport regimes separated by a critical threshold, with a markedly intensified flow in the second regime. It is demonstrated that rising electric field strengths significantly enhance water diffusion coefficients, supported by a detailed analysis of fluid hydration structures, the potential of mean force (PMF), and local stress tensors. Due to the applied electric field strength, the motion of ions and water accelerates, leading to the redistribution of ions and intensification of electrostatic forces. This expands the thickness of the electric double layer (EDL) and amplifies fluid diffusivity, thereby enhancing nanoscale fluid activity. These insights enhance the molecular-level understanding of EOF and define the stability of flow regimes, providing valuable guidelines for advancing nanofluidic technologies, such as drug delivery systems and lab-on-a-chip devices.

Diffusion Coefficients of Coated Plasmonic Nanoparticles in Viscous Environment.

The Stokes-Einstein relationship (SER) is not valid anymore in polymeric solutions for nanoparticles. It is thus important to characterize their diffusion properties to get a finer understanding of their behavior and to better tune their attributes for biomedical applications. The diffusion of gold and silver nanoparticles with citrate, hyaluronic acid, methyl-polyethylene glycol, and antibody-polyethylene glycol coatings is studied in hyaluronic-based viscous solutions. The diffusion coefficient D is estimated from the Brownian motion thanks to a cost-effective side-illumination device. It is determined that the nanoparticles (hydrodynamic radius rh: 30-135 nm) diffuse up to 4-5 times faster than expected using the SER with a macroscopic viscosity from 1 to 30 mPa·s. It is shown that the adapted Huggins equation is a good model to describe the diffusion behavior of nanoparticles using an effective viscosity ηeff given by l n ( η e f f η s ) = k ( R e f f E ) a $ln\ ( {\frac{{{{\eta }_{eff}}}}{{{{\eta }_s}}}} ) = \ k{{( {\ \frac{{{{R}_{eff}}}}{E}} )}^a}$ where R e f f - 2 = r h - 2 + R h - 2 $R_{eff}^{ - 2} = r_h^{ - 2}\ + R_h^{ - 2}$ where E is the polymer correlation length, Rh the polymer hydrodynamic radius and ηs the solvent viscosity. The values of k and a are given and allow to obtain D with an error of 10-20%. The impact of chemical interactions on the model parameter values are also highlighted, especially due to electrostatic interactions between the polymer and the nanoparticles.

Folding speeds of helical membrane proteins.

Membrane proteins play key roles in human health, contributing to cellular signaling, ATP synthesis, immunity, and metabolite transport. Protein folding is the pivotal early step for their proper functioning. Understanding how this class of proteins adopts their native folds could potentially aid in drug design and therapeutic interventions for misfolding diseases. It is an essential piece in the whole puzzle to untangle their kinetic complexities, such as how rapid membrane proteins fold, how their folding speeds are influenced by changing conditions, and what mechanisms are at play. This review explores the folding speed aspect of multipass α-helical membrane proteins, encompassing plausible folding scenarios based on the timing and stability of helix packing interactions, methods for characterizing the folding time scales, relevant folding steps and caveats for interpretation, and potential implications. The review also highlights the recent estimation of the so-called folding speed limit of helical membrane proteins and discusses its consequent impact on the current picture of folding energy landscapes.

Reversibly Tuning the Viscosity of Peptide-Based Solutions Using Visible Light.

Light can be used to design stimuli-responsive systems. We induce transient changes in the assembly of a low molecular weight gelator solution using a merocyanine photoacid. Through our approach, reversible viscosity changes can be achieved via irradiation, delivering systems where flow can be controlled non-invasively on demand.

Quantitative Characterization of RCA-Based DNA Hydrogels - Towards Rational Materials Design.

DNA hydrogels hold significant promise for biomedical applications and can be synthesized through enzymatic Rolling Circle Amplification (RCA). Due to the exploratory nature of this emerging field, standardized RCA protocols specifying the impact of reaction parameters are currently lacking. This study varied template sequences and reagent concentrations, evaluating RCA synthesis efficiency and hydrogel mechanical properties through quantitative PCR (qPCR) and indentation measurements, respectively. Primer concentration and stabilizing additives showed minimal impact on RCA efficiency, while changes in polymerase and nucleotide concentrations had a stronger effect. Concentration of the circular template exerted the greatest influence on RCA productivity. An exponential correlation between hydrogel viscosity and DNA amplicon concentration was observed, with nucleobase sequence significantly affecting both amplification efficiency and material properties, particularly through secondary structures. This study suggests that combining high-throughput experimental methods with structural folding prediction offers a viable approach for systematically establishing structure-property relationships, aiding the rational design of DNA hydrogel material systems.

Engineering Phi29-DNAP Variants for Customized DNA Hydrogel Materials.

DNA hydrogels, which hold potential for use in medicine, biosensors, and tissue engineering, can be produced through enzymatic rolling circle amplification (RCA) using phi29 DNA polymerase (DNAP). This paper introduces new DNAP variants designed for RCA-based DNA hydrogel production, featuring enzymes with modified DNA binding, enhanced thermostability, reduced exonuclease activity, and protein tags for fluorescence detection or specific immobilization. We evaluated these enzymes by quantifying DNA output via quantitative PCR (qPCR) and assessing hydrogel mechanical properties through micromechanical indentation. The results showed that most variants generated similar DNA amounts and hydrogels with comparable mechanical properties. Additionally, all variants successfully incorporated non-natural nucleotides, such as base-modified dGTP derivatives and 2'-fluoro-dGTP, during RCA. This study's robust analytical approach offers a strong foundation for selecting new enzymes and producing DNA hydrogels with tailored material properties.

Customized Modification of Welan Gum Properties Through Controllable Grafting of Acrylamide.

Welan gum (WG) has a wide range of applications, but it is not yet suitable for applications such as oil recovery profile control that have complex requirements for viscosity, gelation properties, and so forth. Grafting modification is an important strategy for improving the property of WG, but there are few reports on controllable modification of WG to customize it for specific application. Acrylamide (AM) dosage was identified as the key factor affecting the grafting ratio of AM onto WG by a uniform experimental design. The grafting ratio can be directly adjusted between 99% and 378% based on the positive correlation with dosage of AM, and viscosity can be adjusted between 206 and 327 mPa s based on the negative correlation with grafting ratio. The 50% weight loss temperature of W11 with a grafting ratio of 110% raised from 314 to 336°C after grafting. The viscosity of the hydrogel formed with WG11 reached 15,654 mPa s, nearly nine times higher than that of unmodified WG. In addition, the gelation time can be controlled within 5 days, so that it can be injected to the optimal area in oilfield profile, avoiding pipeline blockage. This study enables adjusting viscosity of WG grafted with AM by controlling the grafting rate, and enhances gelation performance and thermal stability of WG, which will expand the application of WG in oil recovery and other fields.

A computational model for single cell Lamin-A structural organization after microfluidic compression.

In recent years, nuclear mechanobiology gained a lot of attention for the study of cell responses to external cues like adhesive forces, applied compression, and/or shear-stresses. In details, the Lamin-A protein-as major constituent of the cell nucleus structure-plays a crucial role in the overall nucleus mechanobiological response. However, modeling and analysis of Lamin-A protein organization upon rapid compression conditions in microfluidics are still difficult to be performed. Here, we introduce the possibility to control an applied microfluidic compression on single cells, deforming them up to the nucleus level. In a wide range of stresses (~1-102 kPa) applied on healthy and cancer cells, we report increasing Lamin-A intensities which scale as a power law with the applied compression. Then, an increase up to two times of the nuclear viscosity is measured in healthy cells, due to the modified Lamin-A organization. This is ascribable to the increasing assembly of Lamin-A filament-like branches which increment both in number and elongation (up to branches four-time longer). Moreover, the solution of a computational model of differential equations is presented as a powerful tool for a single cell prediction of the Lamin-A assembly as a function of the applied compression.