A minimal physical model for curvotaxis driven by curved protein complexes at the cell's leading edge.

Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels, or highly curved protrusions of other cells. Recent in vitro experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed "curvotaxis." The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a "minimal cell" model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimal-cell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behavior of this model on different types of curved substrates (sinusoidal, cylinder, and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane-substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.

Physical model of end-diastolic and end-systolic pressure-volume relationships of a heart.

Left ventricular stiffness and contractility, characterized by the end-diastolic pressure-volume relationship (EDPVR) and the end-systolic pressure-volume relationship (ESPVR), are two important indicators of the performance of the human heart. Although much research has been conducted on EDPVR and ESPVR, no model with physically interpretable parameters combining both relationships has been presented, thereby impairing the understanding of cardiac physiology and pathology. Here, we present a model that evaluates both EDPVR and ESPVR with physical interpretations of the parameters in a unified framework. Our physics-based model fits the available experimental data and in silico results very well and outperforms existing models. With prescribed parameters, the new model is used to predict the pressure-volume relationships of the left ventricle. Our model provides a deeper understanding of cardiac mechanics and thus will have applications in cardiac research and clinical medicine.

Universal Velocity Statistics in Decaying Turbulence.

In turbulent flows, kinetic energy is transferred from large spatial scales to small ones, where it is converted to heat by viscosity. For strong turbulence, i.e., high Reynolds numbers, Kolmogorov conjectured in 1941 that this energy transfer is dominated by inertial forces at intermediate spatial scales. Since Kolmogorov's conjecture, the velocity difference statistics in this so-called inertial range have been expected to follow universal power laws for which theoretical predictions have been refined over the years. Here we present experimental results over an unprecedented range of Reynolds numbers in a well-controlled wind tunnel flow produced in the Max Planck Variable Density Turbulence Tunnel. We find that the measured second-order velocity difference statistics become independent of the Reynolds number, suggesting a universal behavior of decaying turbulence. However, we do not observe power laws even at the highest Reynolds number, i.e., at turbulence levels otherwise only attainable in atmospheric flows. Our results point to a Reynolds number-independent logarithmic correction to the classical power law for decaying turbulence that calls for theoretical understanding.

Flagellum-driven cargoes: Influence of cargo size and the flagellum-cargo attachment geometry.

The beating of cilia and flagella, which relies on an efficient conversion of energy from ATP-hydrolysis into mechanical work, offers a promising way to propel synthetic cargoes. Recent experimental realizations of such micro-swimmers, in which micron-sized beads are propelled by isolated and demembranated flagella from the green algae Chlamydomonas reinhardtii (C. reinhardtii), revealed a variety of propulsion modes, depending in particular on the calcium concentration. Here, we investigate theoretically and numerically the propulsion of a bead as a function of the flagellar waveform and the attachment geometries between the bead and the flagellum. To this end, we take advantage of the low Reynolds number of the fluid flows generated by the micro-swimmer, which allows us to neglect fluid inertia. By describing the flagellar waveform as a superposition of a static component and a propagating wave, and using resistive-force theory, we show that the asymmetric sideways attachment of the flagellum to the bead makes a contribution to the rotational velocity of the micro-swimmer that is comparable to the contribution caused by the static component of the flagellar waveform. Remarkably, our analysis reveals the existence of a counter-intuitive propulsion regime in which an increase in the size of the cargo, and hence its drag, leads to an increase in some components of the velocity of the bead. Finally, we discuss the relevance of the uncovered mechanisms for the fabrication of synthetic, bio-actuated medical micro-robots for targeted drug delivery.

A multi-layered strategy for COVID-19 infection prophylaxis in schools: A review of the evidence for masks, distancing, and ventilation.

Implications for the academic and interpersonal development of children and adolescents underpin a global political consensus to maintain in-classroom teaching during the ongoing COVID-19 pandemic. In support of this aim, the WHO and UNICEF have called for schools around the globe to be made safer from the risk of COVID-19 transmission. Detailed guidance is needed on how this goal can be successfully implemented in a wide variety of educational settings in order to effectively mitigate impacts on the health of students, staff, their families, and society. This review provides a comprehensive synthesis of current scientific evidence and emerging standards in relation to the use of layered prevention strategies (involving masks, distancing, and ventilation), setting out the basis for their implementation in the school environment. In the presence of increasingly infectious SARS-Cov-2 variants, in-classroom teaching can only be safely maintained through a layered strategy combining multiple protective measures. The precise measures that are needed at any point in time depend upon a number of dynamic factors, including the specific threat-level posed by the circulating variant, the level of community infection, and the political acceptability of the resultant risk. By consistently implementing appropriate prophylaxis measures, evidence shows that the risk of infection from in-classroom teaching can be dramatically reduced. Current studies indicate that wearing high-quality masks and regular testing are amongst the most important measures in preventing infection transmission; whilst effective natural and mechanical ventilation systems have been shown to reduce infection risks in classrooms by over 80%.

A Synthetic Minimal Beating Axoneme.

Cilia and flagella are beating rod-like organelles that enable the directional movement of microorganisms in fluids and fluid transport along the surface of biological organisms or inside organs. The molecular motor axonemal dynein drives their beating by interacting with microtubules. Constructing synthetic beating systems with axonemal dynein capable of mimicking ciliary beating still represents a major challenge. Here, the bottom-up engineering of a sustained beating synthoneme consisting of a pair of microtubules connected by a series of periodic arrays of approximately eight axonemal dyneins is reported. A model leads to the understanding of the motion through the cooperative, cyclic association-dissociation of the molecular motor from the microtubules. The synthoneme represents a bottom-up self-organized bio-molecular machine at the nanoscale with cilia-like properties.

Bio-hybrid micro-swimmers propelled by flagella isolated from C. reinhardtii.

Bio-hybrid micro-swimmers, composed of biological entities integrated with synthetic constructs, actively transport cargo by converting chemical energy into mechanical work. Here, using isolated and demembranated flagella from green algae Chlamydomonas reinhardtii (C. reinhardtii), we build efficient axonemally-driven micro-swimmers that consume ATP to propel micron-sized beads. Depending on the calcium concentration, we observed two main classes of motion: whereas beads move along curved trajectories at calcium concentrations below 0.03 mM, they are propelled along straight paths when the calcium concentration increases. In this regime, they reached velocities of approximately 20 µm s-1, comparable to human sperm velocity in vivo. We relate this transition to the properties of beating axonemes, in particular the reduced static curvature with increasing calcium concentration. Our designed system has potential applications in the fabrication of synthetic micro-swimmers, and in particular, bio-actuated medical micro-robots for targeted drug delivery.

Aspect Ratio Dependence of Heat Transfer in a Cylindrical Rayleigh-Bénard Cell.

While the heat transfer and the flow dynamics in a cylindrical Rayleigh-Bénard (RB) cell are rather independent of the aspect ratio Γ (diameter/height) for large Γ, a small-Γ cell considerably stabilizes the flow and thus affects the heat transfer. Here, we first theoretically and numerically show that the critical Rayleigh number for the onset of convection at given Γ follows Ra_{c,Γ}∼Ra_{c,∞}(1+CΓ^{-2})^{2}, with C≲1.49 for Oberbeck-Boussinesq (OB) conditions. We then show that, in a broad aspect ratio range (1/32)≤Γ≤32, the rescaling Ra→Ra_{ℓ}≡Ra[Γ^{2}/(C+Γ^{2})]^{3/2} collapses various OB numerical and almost-OB experimental heat transport data Nu(Ra,Γ). Our findings predict the Γ dependence of the onset of the ultimate regime Ra_{u,Γ}∼[Γ^{2}/(C+Γ^{2})]^{-3/2} in the OB case. This prediction is consistent with almost-OB experimental results (which only exist for Γ=1, 1/2, and 1/3) for the transition in OB RB convection and explains why, in small-Γ cells, much larger Ra (namely, by a factor Γ^{-3}) must be achieved to observe the ultimate regime.

Generation of intense dissipation in high Reynolds number turbulence.

Intense fluctuations of energy dissipation rate in turbulent flows result from the self-amplification of strain rate via a quadratic nonlinearity, with contributions from vorticity (via the vortex stretching mechanism) and pressure-Hessian-which are analysed here using direct numerical simulations of isotropic turbulence on up to [Formula: see text] grid points, and Taylor-scale Reynolds numbers in the range 140-1300. We extract the statistics involved in amplification of strain and condition them on the magnitude of strain. We find that strain is self-amplified by the quadratic nonlinearity, and depleted via vortex stretching, whereas pressure-Hessian acts to redistribute strain fluctuations towards the mean-field and hence depletes intense strain. Analysing the intense fluctuations of strain in terms of its eigenvalues reveals that the net amplification is solely produced by the third eigenvalue, resulting in strong compressive action. By contrast, the self-amplification acts to deplete the other two eigenvalues, whereas vortex stretching acts to amplify them, with both effects cancelling each other almost perfectly. The effect of the pressure-Hessian for each eigenvalue is qualitatively similar to that of vortex stretching, but significantly weaker in magnitude. Our results conform with the familiar notion that intense strain is organized in sheet-like structures, which are in the vicinity of, but never overlap with tube-like regions of intense vorticity due to fundamental differences in their amplifying mechanisms. This article is part of the theme issue 'Scaling the turbulence edifice (part 1)'.

An upper bound on one-to-one exposure to infectious human respiratory particles.

There is ample evidence that masking and social distancing are effective in reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. However, due to the complexity of airborne disease transmission, it is difficult to quantify their effectiveness, especially in the case of one-to-one exposure. Here, we introduce the concept of an upper bound for one-to-one exposure to infectious human respiratory particles and apply it to SARS-CoV-2. To calculate exposure and infection risk, we use a comprehensive database on respiratory particle size distribution; exhalation flow physics; leakage from face masks of various types and fits measured on human subjects; consideration of ambient particle shrinkage due to evaporation; and rehydration, inhalability, and deposition in the susceptible airways. We find, for a typical SARS-CoV-2 viral load and infectious dose, that social distancing alone, even at 3.0 m between two speaking individuals, leads to an upper bound of 90% for risk of infection after a few minutes. If only the susceptible wears a face mask with infectious speaking at a distance of 1.5 m, the upper bound drops very significantly; that is, with a surgical mask, the upper bound reaches 90% after 30 min, and, with an FFP2 mask, it remains at about 20% even after 1 h. When both wear a surgical mask, while the infectious is speaking, the very conservative upper bound remains below 30% after 1 h, but, when both wear a well-fitting FFP2 mask, it is 0.4%. We conclude that wearing appropriate masks in the community provides excellent protection for others and oneself, and makes social distancing less important.

Pulsed low-energy stimulation initiates electric turbulence in cardiac tissue.

Interruptions in nonlinear wave propagation, commonly referred to as wave breaks, are typical of many complex excitable systems. In the heart they lead to lethal rhythm disorders, the so-called arrhythmias, which are one of the main causes of sudden death in the industrialized world. Progress in the treatment and therapy of cardiac arrhythmias requires a detailed understanding of the triggers and dynamics of these wave breaks. In particular, two very important questions are: 1) What determines the potential of a wave break to initiate re-entry? and 2) How do these breaks evolve such that the system is able to maintain spatiotemporally chaotic electrical activity? Here we approach these questions numerically using optogenetics in an in silico model of human atrial tissue that has undergone chronic atrial fibrillation (cAF) remodelling. In the lesser studied sub-threshold illumination régime, we discover a new mechanism of wave break initiation in cardiac tissue that occurs for gentle slopes of the restitution characteristics. This mechanism involves the creation of conduction blocks through a combination of wavefront-waveback interaction, reshaping of the wave profile and heterogeneous recovery from the excitation of the spatially extended medium, leading to the creation of re-excitable windows for sustained re-entry. This finding is an important contribution to cardiac arrhythmia research as it identifies scenarios in which low-energy perturbations to cardiac rhythm can be potentially life-threatening.

Fabrication of freestanding Pt nanowires for use as thermal anemometry probes in turbulence measurements.

We report a robust fabrication method for patterning freestanding Pt nanowires for use as thermal anemometry probes for small-scale turbulence measurements. Using e-beam lithography, high aspect ratio Pt nanowires (~300 nm width, ~70 µm length, ~100 nm thickness) were patterned on the surface of oxidized silicon (Si) wafers. Combining wet etching processes with dry etching processes, these Pt nanowires were successfully released, rendering them freestanding between two silicon dioxide (SiO2) beams supported on Si cantilevers. Moreover, the unique design of the bridge holding the device allowed gentle release of the device without damaging the Pt nanowires. The total fabrication time was minimized by restricting the use of e-beam lithography to the patterning of the Pt nanowires, while standard photolithography was employed for other parts of the devices. We demonstrate that the fabricated sensors are suitable for turbulence measurements when operated in constant-current mode. A robust calibration between the output voltage and the fluid velocity was established over the velocity range from 0.5 to 5 m s-1 in a SF6 atmosphere at a pressure of 2 bar and a temperature of 21 °C. The sensing signal from the nanowires showed negligible drift over a period of several hours. Moreover, we confirmed that the nanowires can withstand high dynamic pressures by testing them in air at room temperature for velocities up to 55 m s-1.

Electrophysiological Characterization of Human Atria: The Understated Role of Temperature.

Ambient temperature has a profound influence on cellular electrophysiology through direct control over the gating mechanisms of different ion channels. In the heart, low temperature is known to favor prolongation of the action potential. However, not much is known about the influence of temperature on other important characterization parameters such as the resting membrane potential (RMP), excitability, morphology and characteristics of the action potential (AP), restitution properties, conduction velocity (CV) of signal propagation, etc. Here we present the first, detailed, systematic in silico study of the electrophysiological characterization of cardiomyocytes from different regions of the normal human atria, based on the effects of ambient temperature (5-50°C). We observe that RMP decreases with increasing temperature. At ~ 48°C, the cells lose their excitability. Our studies show that different parts of the atria react differently to the same changes in temperature. In tissue simulations a drop in temperature correlated positively with a decrease in CV, but the decrease was region-dependent, as expected. In this article we show how this heterogeneous response can provide an explanation for the development of a proarrhythmic substrate during mild hypothermia. We use the above concept to propose a treatment strategy for atrial fibrillation that involves severe hypothermia in specific regions of the heart for a duration of only ~ 200 ms.

Risk assessment for airborne disease transmission by poly-pathogen aerosols.

In the case of airborne diseases, pathogen copies are transmitted by droplets of respiratory tract fluid that are exhaled by the infectious that stay suspended in the air for some time and, after partial or full drying, inhaled as aerosols by the susceptible. The risk of infection in indoor environments is typically modelled using the Wells-Riley model or a Wells-Riley-like formulation, usually assuming the pathogen dose follows a Poisson distribution (mono-pathogen assumption). Aerosols that hold more than one pathogen copy, i.e. poly-pathogen aerosols, break this assumption even if the aerosol dose itself follows a Poisson distribution. For the largest aerosols where the number of pathogen in each aerosol can sometimes be several hundred or several thousand, the effect is non-negligible, especially in diseases where the risk of infection per pathogen is high. Here we report on a generalization of the Wells-Riley model and dose-response models for poly-pathogen aerosols by separately modeling each number of pathogen copies per aerosol, while the aerosol dose itself follows a Poisson distribution. This results in a model for computational risk assessment suitable for mono-/poly-pathogen aerosols. We show that the mono-pathogen assumption significantly overestimates the risk of infection for high pathogen concentrations in the respiratory tract fluid. The model also includes the aerosol removal due to filtering by the individuals which becomes significant for poorly ventilated environments with a high density of individuals, and systematically includes the effects of facemasks in the infectious aerosol source and sink terms and dose calculations.

Experimental observation of the elastic range scaling in turbulent flow with polymer additives.

A minute amount of long-chain flexible polymer dissolved in a turbulent flow can drastically change flow properties, such as reducing the drag and enhancing mixing. One fundamental riddle is how these polymer additives interact with the eddies of different spatial scales existing in the turbulent flow and, in turn, alter the turbulence energy transfer. Here, we show how turbulent kinetic energy is transferred through different scales in the presence of the polymer additives. In particular, we observed experimentally the emerging of a previously unidentified scaling range, referred to as the elastic range, where increasing amount of energy is transferred by the elasticity of the polymers. In addition, the existence of the elastic range prescribes the scaling of high-order velocity statistics. Our findings have important implications to many turbulence systems, such as turbulence in plasmas or superfluids where interaction between turbulent eddies and other nonlinear physical mechanisms are often involved.

Light-Powered Reactivation of Flagella and Contraction of Microtubule Networks: Toward Building an Artificial Cell.

Artificial systems capable of self-sustained movement with self-sufficient energy are of high interest with respect to the development of many challenging applications, including medical treatments, but also technical applications. The bottom-up assembly of such systems in the context of synthetic biology is still a challenging task. In this work, we demonstrate the biocompatibility and efficiency of an artificial light-driven energy module and a motility functional unit by integrating light-switchable photosynthetic vesicles with demembranated flagella. The flagellar propulsion is coupled to the beating frequency, and dynamic ATP synthesis in response to illumination allows us to control beating frequency of flagella in a light-dependent manner. In addition, we verified the functionality of light-powered synthetic vesicles in in vitro motility assays by encapsulating microtubules assembled with force-generating kinesin-1 motors and the energy module to investigate the dynamics of a contractile filamentous network in cell-like compartments by optical stimulation. Integration of this photosynthetic system with various biological building blocks such as cytoskeletal filaments and molecular motors may contribute to the bottom-up synthesis of artificial cells that are able to undergo motor-driven morphological deformations and exhibit directional motion in a light-controllable fashion.

Self-attenuation of extreme events in Navier-Stokes turbulence.

Turbulent fluid flows are ubiquitous in nature and technology, and are mathematically described by the incompressible Navier-Stokes equations. A hallmark of turbulence is spontaneous generation of intense whirls, resulting from amplification of the fluid rotation-rate (vorticity) by its deformation-rate (strain). This interaction, encoded in the non-linearity of Navier-Stokes equations, is non-local, i.e., depends on the entire state of the flow, constituting a serious hindrance in turbulence theory and even establishing regularity of the equations. Here, we unveil a novel aspect of this interaction, by separating strain into local and non-local contributions utilizing the Biot-Savart integral of vorticity in a sphere of radius R. Analyzing highly-resolved numerical turbulent solutions to Navier-Stokes equations, we find that when vorticity becomes very large, the local strain over small R surprisingly counteracts further amplification. This uncovered self-attenuation mechanism is further shown to be connected to local Beltramization of the flow, and could provide a direction in establishing the regularity of Navier-Stokes equations.

Plasmonic and Semiconductor Nanoparticles Interfere with Stereolithographic 3D Printing.

Two-photon polymerization stereolithographic three-dimensional (3D) printing is used for manufacturing a variety of structures ranging from microdevices to refractive optics. Incorporation of nanoparticles in 3D printing offers huge potential to create even more functional nanocomposite structures. However, this is difficult to achieve since the agglomeration of the nanoparticles can occur. Agglomeration not only leads to an uneven distribution of nanoparticles in the photoresin but also induces scattering of the excitation beam and altered absorption profiles due to interparticle coupling. Thus, it is crucial to ensure that the nanoparticles do not agglomerate during any stage of the process. To achieve noninteracting and well-dispersed nanoparticles on the 3D printing process, first, the stabilization of nanoparticles in the 3D printing resin is indispensable. We achieve this by functionalizing the nanoparticles with surface-bound ligands that are chemically similar to the photoresin that allows increased nanoparticle loadings without inducing agglomeration. By systematically studying the effect of different nanomaterials (Au nanoparticles, Ag nanoparticles, and CdSe/CdZnS nanoplatelets) in the resin on the 3D printing process, we observe that both, material-specific (absorption profiles) and unspecific (radical quenching at nanoparticle surfaces) pathways co-exist by which the photopolymerization procedure is altered. This can be exploited to increase the printing resolution leading to a reduction of the minimum feature size.

Cellular velocity, electrical persistence and sensing in developed and vegetative cells during electrotaxis.

Cells have the ability to detect electric fields and respond to them with directed migratory movement. Investigations identified genes and proteins that play important roles in defining the migration efficiency. Nevertheless, the sensing and transduction mechanisms underlying directed cell migration are still under discussion. We use Dictyostelium discoideum cells as model system for studying eukaryotic cell migration in DC electric fields. We have defined the temporal electric persistence to characterize the memory that cells have in a varying electric field. In addition to imposing a directional bias, we observed that the electric field influences the cellular kinematics by accelerating the movement of cells along their paths. Moreover, the study of vegetative and briefly starved cells provided insight into the electrical sensing of cells. We found evidence that conditioned medium of starved cells was able to trigger the electrical sensing of vegetative cells that would otherwise not orient themselves in the electric field. This observation may be explained by the presence of the conditioned medium factor (CMF), a protein secreted by the cells, when they begin to starve. The results of this study give new insights into understanding the mechanism that triggers the electrical sensing and transduces the external stimulus into directed cell migration. Finally, the observed increased mobility of cells over time in an electric field could offer a novel perspective towards wound healing assays.