The fluidic memristor as a collective phenomenon in elastohydrodynamic networks.

Fluid flow networks are ubiquitous and can be found in a broad range of contexts, from human-made systems such as water supply networks to living systems like animal and plant vasculature. In many cases, the elements forming these networks exhibit a highly non-linear pressure-flow relationship. Although we understand how these elements work individually, their collective behavior remains poorly understood. In this work, we combine experiments, theory, and numerical simulations to understand the main mechanisms underlying the collective behavior of soft flow networks with elements that exhibit negative differential resistance. Strikingly, our theoretical analysis and experiments reveal that a minimal network of nonlinear resistors, which we have termed a 'fluidic memristor', displays history-dependent resistance. This new class of element can be understood as a collection of hysteresis loops that allows this fluidic system to store information, and it can be directly used as a tunable resistor in fluidic setups. Our results provide insights that can inform other applications of fluid flow networks in soft materials science, biomedical settings, and soft robotics, and may also motivate new understanding of the flow networks involved in animal and plant physiology.

Locally optimal geometry for surface-enhanced diffusion.

Molecular diffusion in bulk liquids proceeds according to Fick's law, which stipulates that the particle current is proportional to the conductive area. This constrains the efficiency of filtration systems in which both selectivity and permeability are valued. Previous studies have demonstrated that interactions between the diffusing species and solid boundaries can enhance or reduce particle transport relative to bulk conditions. However, only cases that preserve the monotonic relationship between particle current and conductive area are known. In this paper, we expose a system in which the diffusive current increases when the conductive area diminishes. These examples are based on the century-old theory of a charged particle interacting with an electrical double layer. This surprising discovery could improve the efficiency of filtration and may advance our understanding of biological pore structures.

Elastohydrodynamic autoregulation in soft overlapping channels.

Controlling fluid flow from an unsteady source is a challenging problem that is relevant in both living and man-made systems. Animals have evolved various autoregulatory mechanisms to maintain homeostasis in vital organs. This keeps the influx of nutrients essentially constant and independent of the perfusion pressure. Up to this point, the autoregulation processes have primarily been ascribed to active mechanisms that regulate vessel size, thereby adjusting the hydraulic conductance in response to, e.g., sensing of wall shear stress. We propose an alternative elastohydrodynamic mechanism based on contacting soft vessels. Inspired by Starling's resistor, we combine experiments and theory to study the flow of a viscous liquid through a self-intersecting soft conduit. In the overlapping region, the pressure difference between the two channel segments can cause one pipe segment to dilate while the other is compressed. If the tissue is sufficiently soft, this mode of fluid-structure interactions can lead to flow autoregulation. Our experimental observations compare well to a predictive model based on low-Reynolds-number fluid flow and linear elasticity. Implications for conduit arrangement and passive autoregulation in organs and limbs are discussed.

Astrocyte endfeet may theoretically act as valves to convert pressure oscillations to glymphatic flow.

The glymphatic system of cerebrospinal fluid transport through the perivascular spaces of the brain has been implicated in metabolic waste clearance, neurodegenerative diseases and in acute neurological disorders such as stroke and cardiac arrest. In other biological low-pressure fluid pathways such as in veins and the peripheral lymphatic system, valves play an important role in ensuring the flow direction. Though fluid pressure is low in the glymphatic system and directed bulk flow has been measured in pial and penetrating perivascular spaces, no valves have yet been identified. Valves, which asymmetrically favour forward flow to backward flow, would imply that the considerable oscillations in blood and ventricle volumes seen in magnetic resonance imaging could cause directed bulk flow. Here, we propose that astrocyte endfeet may act as such valves using a simple elastic mechanism. We combine a recent fluid mechanical model of viscous flow between elastic plates with recent measurements of in vivo elasticity of the brain to predict order of magnitude flow-characteristics of the valve. The modelled endfeet are effective at allowing forward while preventing backward flow.

Pavement cells distinguish touch from letting go.

A micro-cantilever technique applied to individual leaf epidermis cells of intact Arabidopsis thaliana and Nicotiana tabacum synthesizing genetically encoded calcium indicators (R-GECO1 and GCaMP3) revealed that compressive forces induced local calcium peaks that preceded delayed, slowly moving calcium waves. Releasing the force evoked significantly faster calcium waves. Slow waves were also triggered by increased turgor and fast waves by turgor drops in pressure probe tests. The distinct characteristics of the wave types suggest different underlying mechanisms and an ability of plants to distinguish touch from letting go.

Diversity of funnel plasmodesmata in angiosperms: the impact of geometry on plasmodesmal resistance.

In most plant tissues, threads of cytoplasm, or plasmodesmata, connect the protoplasts via pores in the cell walls. This enables symplasmic transport, for instance in phloem loading, transport and unloading. Importantly, the geometry of the wall pore limits the size of the particles that may be transported, and also (co-)defines plasmodesmal resistance to diffusion and convective flow. However, quantitative information on transport through plasmodesmata in non-cylindrical cell wall pores is scarce. We have found conical, funnel-shaped cell wall pores in the phloem-unloading zone in growing root tips of five eudicot and two monocot species, specifically between protophloem sieve elements and phloem pole pericycle cells. 3D reconstructions by electron tomography suggested that funnel plasmodesmata possess a desmotubule but lack tethers to fix it in a central position. Model calculations showed that both diffusive and hydraulic resistance decrease drastically in conical and trumpet-shaped cell wall pores compared with cylindrical channels, even at very small opening angles. Notably, the effect on hydraulic resistance was relatively larger. We conclude that funnel plasmodesmata generally are present in specific cell-cell interfaces in angiosperm roots, where they appear to facilitate symplasmic phloem unloading. Interestingly, cytosolic sleeves of most plasmodesmata reported in the literature do not resemble annuli of constant diameter but possess variously shaped widenings. Our evaluations suggest that widenings too small for unambiguous identification on electron micrographs may drastically reduce the hydraulic and diffusional resistance of these pores. Consequently, theoretical models assuming cylindrical symmetries will underestimate plasmodesmal conductivities.

Sugar loading is not required for phloem sap flow in maize plants.

Phloem transport of photoassimilates from leaves to non-photosynthetic organs, such as the root and shoot apices and reproductive organs, is crucial to plant growth and yield. For nearly 90 years, evidence has been generally consistent with the theory of a pressure-flow mechanism of phloem transport. Central to this hypothesis is the loading of osmolytes, principally sugars, into the phloem to generate the osmotic pressure that propels bulk flow. Here we used genetic and light manipulations to test whether sugar import into the phloem is required as the driving force for phloem sap flow. Using carbon-11 radiotracer, we show that a maize sucrose transporter1 (sut1) loss-of-function mutant has severely reduced export of carbon from photosynthetic leaves (only ~4% of the wild type level). Yet, the mutant remarkably maintains phloem pressure at ~100% and sap flow speeds at ~50-75% of those of wild type. Potassium (K+) abundance in the phloem was elevated in sut1 mutant leaves. Fluid dynamic modelling supports the conclusion that increased K+ loading compensated for decreased sucrose loading to maintain phloem pressure, and thereby maintained phloem transport via the pressure-flow mechanism. Furthermore, these results suggest that sap flow and transport of other phloem-mobile nutrients and signalling molecules could be regulated independently of sugar loading into the phloem, potentially influencing carbon-nutrient homoeostasis and the distribution of signalling molecules in plants encountering different environmental conditions.

The impact of partial-oral endocarditis treatment on anxiety and depression in the POET trial.

BACKGROUND: The Partial-Oral versus Intravenous Antibiotic Treatment of Endocarditis Trial (POET) found that partial-oral outpatient treatment was non-inferior to conventional in-hospital intravenous treatment in patients with left-sided infective endocarditis. We examined the impact of treatment strategy on levels of anxiety and depression. METHODS: Patients completed the Hospital Anxiety and Depression Scale (HADS) at randomization, at antibiotic completion, and after month 3 and month 6. Changes in anxiety and depression (each subdimension 0-21, high scores indicating worse) were calculated using a repeated measure analysis of covariance model with primary assessment after 6 months. Change in score of 1.7 represented a minimal clinical important difference (MCID). RESULTS: Among the 400 patients enrolled in the POET trial, 263 (66%) completed HADS at randomization with reassessment rates of 86-87% at the three subsequent timepoints. Patients in the partial-oral group and the intravenous group had similar improvements after 6 months in levels of anxiety (-1.8 versus -1.6, P = 0.62) and depression (-2.1 versus -1.9, P = 0.63), although patients in the partial-oral group had numerically lower levels of anxiety and depression throughout. An improvement in MCID scores after 6 months was reported by 47% versus 45% (p = 0.80) patients for anxiety and by 51% versus 54% (p = 0.70) for depression. CONCLUSION: Patients with endocarditis receiving partial-oral outpatient treatment reported similar significant improvements in anxiety and depression at 6 months, as compared to conventionally treated, but numerically lower levels throughout. These findings support the usefulness of partial-oral treatment.

Concentration-Responsive Soft Valve for Osmotic Flow Control.

We propose a novel osmotic soft valve consisting of an osmosis membrane and hydrogel films. In our osmotic valve system, material selectivity is determined by the osmosis membrane, and the hydrogel film, which deforms depending on the ion concentration of the surrounding solution, controls the passage area of the membrane. Independently controlling the material selectivity and permeability allowed us to design an osmotic soft valve with an osmotic flow rate that increases with osmotic pressure at low pressures but decreases with osmotic pressure at high pressures. We demonstrate a representative application of our hydrogel valve system in a portable power generator utilizing reverse electrodialysis (RED). As the permeability varied with concentration, the hydrogel valve was able to maintain the electric power of the RED for 30 min with only an ∼10% change. Our study provides techniques to build osmotic soft valves that can serve as gating membranes in various osmosis and dialysis systems.

Neural networks and robotic microneedles enable autonomous extraction of plant metabolites.

Plant metabolites comprise a wide range of extremely important chemicals. In many cases, like savory spices, they combine distinctive functional properties-deterrence against herbivory-with an unmistakable flavor. Others have remarkable therapeutic qualities, for instance, the malaria drug artemisinin, or mechanical properties, for example natural rubber. We present a breakthrough in plant metabolite extraction technology. Using a neural network, we teach a computer how to recognize metabolite-rich cells of the herbal plant rosemary (Rosmarinus officinalis) and automatically extract the chemicals using a microrobot while leaving the rest of the plant undisturbed. Our approach obviates the need for chemical and mechanical separation and enables the extraction of plant metabolites that currently lack proper methods for efficient biomass use. Computer code required to train the neural network, identify regions of interest, and control the micromanipulator is available as part of the Supplementary Material.

Viscous energy dissipation in slender channels with porous or semipermeable walls.

We study the viscous dissipation in pipe flows in long channels with porous or semipermeable walls, taking into account both the dissipation in the bulk of the channel and in the pores. We give simple closed-form expressions for the dissipation in terms of the axially varying flow rate Q(x) and the pressure p(x), generalizing the well-known expression W[over ̇]=QΔp=RQ^{2} for the case of impenetrable walls with constant Q, pressure difference Δp between the ends of the pipe and resistance R. When the pressure p_{0} outside the pipe is constant, the result is the straightforward generalization W[over ̇]=Δ[(p-p_{0})Q]. Finally, applications to osmotic flows are considered.

Plasmodesmata and the problems with size: Interpreting the confusion.

Plant tissues exhibit a symplasmic organization; the individual protoplasts are connected to their neighbors via cytoplasmic bridges that extend through pores in the cell walls. These bridges may have diameters of a micrometer or more, as in the sieve pores of the phloem, but in most cell types they are smaller. Historically, botanists referred to cytoplasmic bridges of all sizes as plasmodesmata. The meaning of the term began to shift when the transmission electron microscope (TEM) became the preferred tool for studying these structures. Today, a plasmodesma is widely understood to be a 'nano-scale' pore. Unfortunately, our understanding of these nanoscopic channels suffers from methodological limitations. This is exemplified by the fact that state-of-the-art EM techniques appear to reveal plasmodesmal pore structures that are much smaller than the tracer molecules known to diffuse through these pores. In general, transport processes in pores that have dimensions in the size range of the transported molecules are governed by different physical parameters than transport process in the macroscopic realm. This can lead to unexpected effects, as experience in nanofluidic technologies demonstrates. Our discussion of problems of size in plasmodesma research leads us to conclude that the field will benefit from technomimetic reasoning - the utilization of concepts developed in applied nanofluidics for the interpretation of biological systems.

Distribution and prognostic value of left ventricular global longitudinal strain in elderly patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve replacement.

AIMS: The aim of present study was to examine the preoperative prevalence and distribution of impaired left ventricular global longitudinal strain (LVGLS) in elderly patients with symptomatic aortic stenosis (AS) undergoing transcutaneous aortic valve replacement (TAVR) and to determine the predictive value of LVGLS on survival. METHODS: We included 411 patients with symptomatic severe AS treated with TAVR during a 5-year period, where a baseline echocardiography including LVGLS assessment was available. RESULTS: Mean age was 80.1 ± 7.1 years and aortic valve area (AVA) index 0.4 ± 0.1 cm2. 78 patients died during a median follow-up of 762 days. Mean left ventricular ejection fraction (LVEF) was 50 ± 13% and mean LVGLS was - 14.0%. LVEF was preserved in 60% of patients, while impaired LVGLS > - 18% was seen in 75% of the patients. Previous myocardial infarction, LVEF < 50%, LVGLS > - 14%, low gradient AS (< 4.0 m/s), tricuspid regurgitant gradient > 30 mmHg were identified as significant univariate predictors of all-cause mortality. On multivariate analysis LVGLS > - 14% (HR 1.79 [1.02-3.14], p = 0.04) was identified as the only independent variable associated with all-cause mortality. Reduced survival was observed with an impaired LVGLS > - 14% in the total population (p < 0.002) but also in patients with high AS gradient with preserved LVEF. LVGLS provided incremental prognostic value with respect to clinical characteristics, AVA and LVEF (χ2 19.9, p = 0.006). CONCLUSIONS: In patients with symptomatic AS undergoing TAVR, impaired LVGLS was highly prevalent despite preserved LVEF. LVGLS > - 14% was an independent predictor of all-cause mortality, and survival was reduced if LVGLS > - 14%.

Bending and Stretching of Soft Pores Enable Passive Control of Fluid Flows.

Programmable valves and actuators are widely used in man-made systems to provide sophisticated control of fluid flows. In nature, however, this process is frequently achieved using passive soft materials. Here we study how elastic deformations of cylindrical pores embedded in a flexible membrane enable passive flow control. We develop biomimetic valves with variable pore radius, membrane radius, and thickness. Our experiments reveal a mechanism where small deformations bend the membrane and constrict the pore-thus reducing flow-while larger deformations stretch the membrane, expand the pore, and enhance flow. We develop a theory capturing this highly nonmonotonic behavior, and validate the scaling across a broad range of material and geometric parameters. Our results suggest that intercompartmental flow control in living systems can be encoded entirely in the physical attributes of soft materials. Moreover, this design could enable autonomous flow control in man-made systems.

Directionality of Plasmodesmata-Mediated Transport in Arabidopsis Leaves Supports Auxin Channeling.

The plant hormone auxin serves as central regulator of growth and development. Auxin transporters in the plasma membrane are assumed to define tissue-level patterns of auxin distribution [1, 2]. However, auxin is small enough to diffuse through the plasmodesmata that connect neighboring cells [3], presenting an alternative pathway, whose contribution to auxin transport remained largely unexplored [4]. Here, photoactivation microscopy [5, 6] was used to measure the capacity for small-molecule diffusion in the epidermis of Arabidopsis thaliana leaves. In the elongated epidermis cells covering the midrib and petiole, the plasmodesmata-mediated cell-wall permeability was found to be several times higher in the longitudinal than in the transverse direction. The physiological relevance of this asymmetry was tested through quantification of the shade-avoidance response, which depends on auxin transport from the leaf tip to the petiole in the abaxial side of the leaf [7], with the hypothesis that directionality of diffusion supplements transporter-mediated auxin movement [8]. Triggering the response by auxin application at the tip led to stronger leaf movement in wild-type plants than in gsl8 mutants [9], which lack the callose synthase necessary to establish directionality. The results match the predictions of a mathematical model of auxin transport based on the permeabilities measured in wild-type and mutant plants. It is concluded that plasmodesmata permeability can be selectively modulated within a plant cell and that the conferred directionality in diffusion can influence the tissue-specific distribution patterns of small molecules, like auxin. VIDEO ABSTRACT.

A design principle of root length distribution of plants.

Shaping a plant root into an ideal structure for water capture is increasingly important for sustainable agriculture in the era of global climate change. Although the current genetic engineering of crops favours deep-reaching roots, here we show that nature has apparently adopted a different strategy of shaping roots. We construct a mathematical model for optimal root length distribution by considering that plants seek maximal water uptake at the metabolic expenses of root growth. Our theory finds a logarithmic decrease of root length density with depth to be most beneficial for efficient water uptake, which is supported by biological data as well as our experiments using root-mimicking network systems. Our study provides a tool to gauge the relative performance of root networks in transgenic plants engineered to endure a water deficit. Moreover, we lay a fundamental framework for mechanical understanding and design of water-absorptive growing networks, such as medical and industrial fluid transport systems and soft robots, which grow in porous media including soils and biotissues.

Fungal artillery of zombie flies: infectious spore dispersal using a soft water cannon.

Dead sporulating female fly cadavers infected by the house fly-pathogenic fungus Entomophthora muscae are attractive to healthy male flies, which by their physical inspection may mechanically trigger spore release and by their movement create whirlwind airflows that covers them in infectious conidia. The fungal artillery of E. muscae protrudes outward from the fly cadaver, and consists of a plethora of micrometric stalks that each uses a liquid-based turgor pressure build-up to eject a jet of protoplasm and the initially attached spore. The biophysical processes that regulate the release and range of spores, however, are unknown. To study the physics of ejection, we design a biomimetic 'soft cannon' that consists of a millimetric elastomeric barrel filled with fluid and plugged with a projectile. We precisely control the maximum pressure leading up to the ejection, and study the cannon efficiency as a function of its geometry and wall elasticity. In particular, we predict that ejection velocity decreases with spore size. The calculated flight trajectories under aerodynamic drag predict that the minimum spore size required to traverse a quiescent layer of a few millimetres around the fly cadaver is approximately 10 µm. This corroborates with the natural size of E. muscae conidia (approx. 27 µm) being large enough to traverse the boundary layer but small enough (less than 40 µm) to be lifted by air currents. Based on this understanding, we show how the fungal spores are able to reach a new host.

Controlling intercellular flow through mechanosensitive plasmodesmata nanopores.

In plants, plasmodesmata (PD) are nanopores that serve as channels for molecular cell-to-cell transport. Precise control of PD permeability is essential to regulate processes such as growth and tissue patterning, photoassimilate distribution and defense against pathogens. Callose deposition modulates PD transport but little is known of the rapid events that lead to PD closure in response to tissue damage or osmotic shock. We propose a mechanism of PD closure as a result of mechanosensing. Pressure forces acting on the dumbbell-shaped ER-desmotubule complex cause it to be displaced from its equilibrium position, thus closing the PD aperture. The filamentous protein tethers that link the plasma membrane to the ER-desmotubule complex play a key role in determining the selectivity of the PD pore. This model of PD control compares favorably with experimental data on the pressure-generated closure of PD.

Modeling the Hydraulic Conductivity of Phloem Sieve Elements.

Phloem transport of photoassimilates affects nearly all aspects of plant life, from growth to reproduction. This chapter summarizes mathematical techniques to quantify the impact of sieve element anatomy on phloem transport processes.